Stem/leaf desiccant

ABSTRACT

A stem/leaf desiccant for crop plants which comprises as an active ingredient, a compound of formula (I):  
                 
 
     wherein X represent CH or nitrogen; Z represents halogen; A represents oxygen, sulfur, or NH; R 1  represents hydroxyl, C 1 -C 7  alkoxy, C 3 -C 7  alkenyloxy, C 3 -C 7  alkynyloxy, C 5 -C 7  cycloalkoxy, {(C 1 -C 7  alkoxy)carbonyl} C 1 -C 3  alkoxy, (C 1 -C 7  alkylamino)oxy, {di(C 1 -C 7  alkyl)amino}oxy, (C 3 -C 7  alkylideneamino)oxy, C 1 -C 7  alkylamino, di(C 1 -C 7  alkyl)amino, C 3 -C 7  alkenylamino, C 3 -C 7  alkynylamino, C 5 -C 7  cycloalkylamino, {(C 1 -C 7  alkoxy)carbonyl} C 1 -C 3  alkylamino, or (C 1 -C 7  alkoxy)amino; R 2  is hydrogen or methyl; and R 3  is hydrogen, halogen, C 1 -C 3  alkyl, or C 1 -C 3  alkoxy;  
     a method for desiccating a crop plant and a method for harvesting a crop by using the stem/leaf desiccant.

TECHNICAL FIELD

[0001] The present invention relates to a stem/leaf desiccant which isused before the harvest of crops such as potato, sunflower, soybean,rape, sorghum and the like, for desiccating the aboveground part of theplants.

BACKGROUND ART

[0002] Desiccants which desiccate the aboveground part of the plantshave been used to make harvest work of crops, such as potato, sunflower,soybean, rape, sorghum and the like, easy. Especially in a case ofmachine harvest, there is an advantage in an easy operation of a harvestmachine and the like. By desiccating aboveground parts of the plants, anoutbreak of plant diseases can be controlled. The crops such assunflower, the crops must be desiccated before pressing oil from thecrops after the harvest. In this case, by spraying the desiccant, whichdesiccate the crop plants before the harvest, to the plants, andlowering the water content of the seeds; the drying cost before pressingoil can be decreased. Also, in a case of soybean, rape and the like, byspraying the desiccant to the plants and accelerating the ripeness ofcrops; the high-quality harvesting which are uniformly ripen can begained.

[0003] Namely, there are some advantages of desiccating these plantsbefore the harvest. Diquat has been used as a desiccant, however therehas been a great demand for higher-performance desiccant.

DISCLOSURE OF INVENTION

[0004] The present inventor has extensively sought for a novel desiccantfor potato, sunflower, soybean, rape, sorghum and the like. As a result,he has found that compounds of formula (I):

[0005] wherein X is CH or nitrogen; Z is halogen; A is oxygen, sulfur,or NH; R¹ is hydroxyl, C₁-C₇ alkoxy, C₃-C₇ alkenyloxy, C₃-C₇ alkynyloxy,C₅-C₇ cycloalkoxy, {(C₁-C₇ alkoxy)carbonyl} C₁-C₃ alkoxy, (C₁-C₇alkylamino)oxy, {di(C₁-C₇ alkyl)amino}oxy, (C₃-C₇ alkylideneamino)oxy,C₁-C₇ alkylamino, di(C₁-C₇ alkyl)amino, C₃-C₇ alkenylamino, C₃-C₇alkynylamino, C₅-C₇ cycloalkylamino, {(C₁-C₇ alkoxy)carbonyl} C₁-C₃alkylamino or (C₁-C₇ alkoxy)amino; R² is hydrogen or methyl; and R³ ishydrogen, halogen, C₁-C₃ alkyl, or C₁-C₃ alkoxy, have an excellentdesiccant effect for the crop plants, thereby completing the presentinvention. That is, the present invention provides the desiccant, whichcomprise compounds (I) as active ingredients and which are used fordesiccating aboveground parts of the plants, such as potato, sunflower,soybean, rape, sorghum and the like, before the harvest of crops thereof(hereinafter referred to as the present desiccant(s)).

BEST MODE FOR CARRYING OUT THE INVENTION

[0006] The present desiccant is typically used in a manner as describedbelow.

[0007] The application time of the present desiccant may change becauseof the weather condition or the crop plants growth condition. Thepresent desiccant is usually applied when the ripening stage of theplants come near after the vegetative growth of the plants, which thepresent desiccant is going to be applied, has finished. If the plantsare potatoes, the present desiccant is preferably applied between a timeof foliage turning yellow and three days before of the harvesting, morepreferably between twenty-one days before and three days before of theharvesting. If the plants are sunflowers, the present desiccant ispreferably applied when the backside of the flowers turn yellow afterthe plants has been ripened; or when a water content of the seeds rangesfrom 20 wt % to 50 wt % when a water content is a reference. If theplants are soybeans, the present desiccant is preferably applied betweena time of leaves turning brown and one-week before of the harvesting. Ifthe plants are rapes, the present desiccant is preferably applied when acolor of the seeds starts to change from green to brown.

[0008] The present desiccant is usually used in the form of variousformulations including emulsifiable concentrates, wettable powders,flowables, and solutions, which can be prepared by mixing the compound(I) with solid carriers, liquid carriers, or other bulking agents, andif necessary, adding surfactants and other auxiliary agents thereto. Inthese formulations, the compounds (I) are usually contained each in anamount of 0.5% to 80% by weight, preferably 1% to 70% by weight.

[0009] The solid carrier used in the formulation may include, forexample, the following materials in fine powder or granular form: clays(e.g., kaolinite, diatomaceous earth, synthetic hydrated silicon oxide,Fubasami clay, bentonite, acid clay); talc and other inorganic minerals(e.g., sericite, quartz powder, sulfur powder, activated carbon, calciumcarbonate); and chemical fertilizers (e.g., ammonium sulfate, ammoniumphosphate, ammonium nitrate, ammonium chloride, urea). The liquidcarrier may include, for example, water; alcohols (e.g., methanol,ethanol); ketones (e.g., acetone, methyl ethyl ketone, cyclohexanone);aromatic hydrocarbons (e.g., toluene, xylene, ethylbenzene,methylnaphthalene); non-aromatic hydrocarbons (e.g., hexane,cyclohexane, kerosine); esters (e.g., ethyl acetate, butyl acetate);nitriles (e.g., acetonitrile, isobutyronitrile); ethers (e.g., dioxane,diisopropyl ether); acid amides (e.g., dimethylformamide,dimethylacetamide); and halogenated hydrocarbons (e.g., dichloroethane,trichloroethylene).

[0010] The surfactant may include, for example, alkyl sulfate salts;alkylsulfonic acid salts; alkylarylsulfonic acid salts; alkyl arylethers and their polyoxyethylene derivatives; polyethylene glycolethers; polyol esters; and sugar alcohol derivatives.

[0011] The other auxiliary agents may include, for example, adhesiveagents and dispersing agents, such as casein, gelatin, polysaccharides(e.g., powdered starch, gum arabic, cellulose derivatives, alginicacid), lignin derivatives, and synthetic water-soluble polymers (e.g.,polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylic acid); andstabilizers such as PAP (isopropyl acid phosphate), BHT(2,6-di-tert-butyl-4-methylphenol), BHA(2-/3-tert-butyl-4-methyoxyphenol), vegetable oils, mineral oils, fattyacids, and fatty acid esters.

[0012] The present desiccant thus formulated is applied to plants afterdiluted with water. The present desiccant can be expected to havefurther enhanced effects by incorporation of tank mix adjuvants in waterused for dilution.

[0013] The application amounts of the compounds (I) may vary with theformulations types, application times, and application places, but areusually in the range of 1 to 500 g/ha, preferably 1 to 100 g/ha.

[0014] In the formula (I), halogen represented by Z refers to fluorine,chlorine, bromine, or iodine;

[0015] C₁-C₇ alkoxy represented by R¹ may include methoxy, ethoxy,propoxy, isopropoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy,pentyloxy, 1-methylbutoxy, 2-methylbutoxy, 3-methylbutoxy,2,2-dimethylpropoxy, hexyloxy, 1-methylpentyloxy, 2-methylpentyloxy,3-methylpentyloxy, 4-methylpentyloxy, 1,2-dimethylbutoxy,1,3-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, andheptyloxy;

[0016] C₃-C₇ alkenyloxy represented by R¹ may include 2-propenyloxy,3-butenyloxy, 4-pentenyloxy, 3-methyl-3-butenyloxy, and3-methyl-2-butenyloxy;

[0017] C₃-C₇ alkynyloxy represented by R¹ may include 2-propynyloxy;

[0018] C₅-C₇ cycloalkoxy represented by R¹ may include cyclopentyloxyand cyclohexyloxy;

[0019] {(C₁-C₇ alkoxy)carbonyl} C₁-C₃ alkoxy represented by R¹ mayinclude methoxycarbonylmethoxy, ethoxycarbonylmethoxy, and1-(methoxycarbonyl)-1-methylethoxy;

[0020] (C₁-C₇ alkylamino)oxy represented by R¹ may include(methylamino)oxy and (ethylamino)oxy;

[0021] {di(C₁-C₇ alkyl)amino}oxy represented by R¹ may include(dimethylamino)oxy and (methylethylamino)oxy;

[0022] (C₃-C₇ alkylideneamino)oxy represented by R¹ may include(isopropylideneamino)oxy;

[0023] C₁-C₇ alkylamino represented by R¹ may include methylamino,ethylamino, propylamino, isopropylamino, butylamino,1-methylpropylamino, 2-methylpropylamino, pentylamino,1-methylbutylamino, 2-methylbutylamino, 3-methylbutylamino,2,2-dimethylpropylamino, and hexylamino;

[0024] di(C₁-C₇ alkyl)amino represented by R¹ may include dimethylaminoand diethylamino;

[0025] C₃-C₇ alkenylamino represented by R¹ may include 2-propenylamino;

[0026] C₃-C₇ alkynylamino represented by R¹ may include 2-propynylamino;

[0027] C₅-C₇ cycloalkylamino represented by R¹ may includecyclopentylamino and cyclohexylamino;

[0028] {(C₁-C₇ alkoxy)carbonyl} C₁-C₃ alkylamino represented by R¹ mayinclude methoxycarbonylmethylamino;

[0029] (C₁-C₇ alkoxy)amino represented by R¹ may include methoxyamino,ethoxyamino, and isopropoxyamino;

[0030] halogen represented by R³ refers to fluorine, chlorine, bromine,or iodine;

[0031] C₁-C₃ alkyl represented by R³ refers to methyl, ethyl, propyl, orisopropyl; and

[0032] C₁-C₃ alkoxy represented by R³ refers to methoxy, ethoxy,propoxy, or isopropoxy.

[0033] In the compounds of formula (I) used as the active ingredients ofthe present desiccant, preferred are those wherein R¹ is methoxy orethoxy; R³ is hydrogen; and/or Z is chlorine or bromine.

[0034] Compounds (I) can be produced, for example, according toproduction processes A to E as described below.

[0035] Production Process A

[0036] wherein X, Z, A, R², and R³ are as defined above.

[0037] Compound (1-1) can be produced by reacting compound (V) with adiazotizing agent (first step), followed by reaction with a halide(second step).

[0038] The reaction in the first step is usually carried out at atemperature range of −20° C. to 20° C., and the reaction time is amoment to 5 hours.

[0039] The diazotizing agent used in the reaction may include nitrousacid (prepared from nitrites such as sodium nitrite, and protonic acidssuch as acetic acid and hydrochloric acid); nitrite esters such asisoamyl nitrite and t-butyl nitrite. The reaction is usually carried outby adding dropwise the diazotizing agent to a mixture of compound (V)and a solvent such as acetic acid, acetonitrile, or water, or preparinga diazotizing agent in the solvent.

[0040] The amounts of reagents are 1 mole of the diazotizing agentrelative to 1 mole of compound (V), which is a theoretical ratio, butmay suitably be changed depending upon the reaction conditions.

[0041] After the reaction in the first step, the reaction mixture isusually used as the starting material in the second step, without beingsubjected to separation.

[0042] The reaction in the second step is usually carried out in therange of 0° C. to 80° C., and the reaction time is a moment to 24 hours.

[0043] The halide used in the reaction may include fluorides (e.g.,tetrafluoroboric acid), chlorides (e.g., copper (I) chloride), bromides(e.g., copper (I) bromide), and iodides (e.g., potassium iodide). Thereaction is usually carried out by adding dropwise the reaction mixtureobtained in the first step to a mixture of a halide and a solvent suchas acetic acid, acetonitrile, or water.

[0044] The amounts of reagents are 1 mole of the halide relative to 1mole of compound (V), which is a theoretical ratio, but may suitably bechanged depending upon the reaction conditions.

[0045] After completion of the reaction, for example, the reactionmixture is poured into water, which is then extracted with an organicsolvent, and the organic layer is concentrated to give a desiredcompound.

[0046] Production Process B

[0047] wherein E is chlorine or bromine; and Z, A, R¹, R², and R³ are asdefined above.

[0048] Compound (1-3) can be produced by reacting compound (VI) withcompound (XXI) in the presence of a base in a solvent.

[0049] The reaction temperature is usually in the range of 0° C. to 150°C., and the reaction time is usually a moment to 24 hours.

[0050] The base used in the reaction may include organic bases such aspyridine, quinoline, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-azabicylco[4.3.0]non-5-ene,1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine,N,N-dimethylaniline, N,N-diethylaniline, triethylamine,tri-n-propylamine, and diisopropylethylamine; and inorganic bases suchas sodium carbonate, potassium carbonate, sodium hydride, and potassiumhydride.

[0051] The solvent used in the reaction may include aromatichydrocarbons such as toluene and xylene; aromatic halogenatedhydrocarbons such as chlorobenzene, dichlorobenzene, andbenzotrifluride; ethers such as diisopropyl ether, methyl t-butyl ether,dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and diglym;ketones such as methyl isobutyl ketone; esters such as ethyl acetate;nitro compounds such as nitromethane; nitrites such as acetonitrile;amides such as N,N-dimethylformamide and N-methyl-2-pyrollidone; sulfurcompounds such as dimethylsulfoxide and sulforane; and mixtures thereof.

[0052] The amounts of reagents are 1 mole of compound (XXI) and 1 moleof the base, relative to 1 mole of compound (VI), which is a theoreticalratio, but may suitably be changed depending upon the reactionconditions.

[0053] After completion of the reaction, for example, the reactionmixture is poured into water, which is then extracted with an organicsolvent, and the organic layer is concentrated to give a desiredcompound. The product may be purified by chromatography,recrystallization, or any other technique.

[0054] Production Process C

[0055] wherein E¹ is a leaving group such as iodine ormethanesulfonyloxy, and X, Z, A, R¹, R², and R³ are as defined above.

[0056] Compound (1-3) can be produced by reacting compound (XXV) withcompound (XXVI) in the presence of a base in a solvent.

[0057] The reaction temperature is usually in the range of 0° C. to 150°C., and the reaction time is usually a moment to 24 hours.

[0058] The base used in the reaction may include organic bases such aspyridine, quinoline, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicylco[4.3.0]non-5-ene,1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine,N,N-dimethylaniline, N,N-diethylaniline, triethylamine,tri-n-propylamine, and diisopropylethylamine; and inorganic bases suchas sodium carbonate, potassium carbonate, sodium hydride, and potassiumhydride.

[0059] The solvent used in the reaction may include aromatichydrocarbons such as toluene and xylene; aromatic halogenatedhydrocarbons such as chlorobenzene, dichlorobenzene, andbenzotrifluoride; ethers such as diisopropyl ether, methyl t-butylether, dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, anddiglym; ketones such as methyl isobutyl ketone; esters such as ethylacetate; nitro compounds such as nitromethane; nitrites such asacetonitrile; amides such as N,N-dimethylformamide andN-methyl-2-pyrollidone; sulfur compounds such as dimethylsulfoxide andsulforane; and mixtures thereof.

[0060] The amounts of reagents are 1 mole of compound (XXVI) and 1 moleof the base, relative to 1 mole of compound (XXVI, which is atheoretical ratio, but may suitably be changed depending upon thereaction conditions.

[0061] After completion of the reaction, for example, the reactionmixture is poured into water, which is then extracted with an organicsolvent, and the organic layer is concentrated to give a desiredcompound. The product may be purified by chromatography,recrystallization, or any other technique.

[0062] Production Process D

[0063] wherein X, Z, A, R¹, R², and R³ are as defined above.

[0064] Compound (1-2) can be produced by reacting compound (1-1) withcompound (XX). The reaction may be carried out in the presence of anacid or a base as a catalyst.

[0065] The reaction temperature is usually in the range of 20° C. to150° C., and the reaction time is usually a moment to 24 hours.

[0066] The acid optionally used may include organic protonic acids suchas methanesulfonic acid; and inorganic protonic acids such as sulfuricacid. The base may include organic bases such as pyridine; and inorganicbases such as sodium carbonate.

[0067] The amounts of reagents are 1 mole to an excess of compound (XX),relative to 1 mole of compound (1-1).

[0068] The reaction may involve the use of a solvent inert thereto. Inthe reaction, the methanol formed as a by-product may be distilled outof the reaction system, so that the rate of the reaction can beincreased.

[0069] After completion of the reaction, for example, the reactionmixture is poured into water, which is then extracted with an organicsolvent, and the organic layer is concentrated to give a desiredcompound. The product may be purified by chromatography,recrystallization, or any other technique.

[0070] Production Process E

[0071] Compound (1-2) can also be produced by reacting compound (1-4)with compound (XX) under the dehydration conditions.

[0072] wherein X, Z, A, R¹, R², and R³ are as defined above.

[0073] Compound (V) can be produced by the process as shown below.

[0074] wherein X, A, R², and R³ are as defined above.

[0075] First step: The step of producing compound (IV) from compound(II) and compound (III).

[0076] Compound (IV) can be produced by reacting compound (II) withcompound (III) in the presence of a base in a solvent.

[0077] The reaction temperature is usually in the range of 0° C. to 150°C., and the reaction time is usually a moment to 24 hours.

[0078] The base used in the reaction may include organic bases such aspyridine, quinoline, N-methylmorpholine, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicylco[4.3.0]non-5-ene,1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine,N,N-dimethylaniline, N,N-diethylaniline, triethylamine,tri-n-propylamine, and diisopropylethylamine; and inorganic bases suchas sodium carbonate, potassium carbonate, sodium hydride, and potassiumhydride.

[0079] The solvent used in the reaction may include aromatichydrocarbons such as toluene and xylene; ethers such as dioxane; amidessuch as N,N-dimethylformamide and N-methyl-2-pyrollidone; sulfurcompounds such as dimethylsulfoxide and sulforane; and mixtures thereof.

[0080] The amounts of reagents are 1 mole of compound (II) and 1 mole ofthe base, relative to 1 mole of compound (III), which is a theoreticalratio, but may suitably be changed depending upon the reactionconditions.

[0081] After completion of the reaction, for example, the reactionmixture is poured into water, which is then extracted with an organicsolvent, and the organic layer is concentrated to give a desiredcompound. The product may be purified by chromatography,recrystallization, or any other technique.

[0082] Second step: The step of producing compound (V) from compound(IV).

[0083] Compound (V) can be produced by reacting compound (IV) with ironpowder in the presence of a protonic acid.

[0084] The reaction temperature is usually in the range of 0° C. to 100°C., and the reaction time is usually a moment to 24 hours.

[0085] The protonic acid used in the reaction may include organicprotonic acids such as acetic acid and propionic acid; and inorganicprotonic acids such as hydrochloric acid.

[0086] The amounts of reagents are 3 moles to an excess of the ironpowder and 3 moles to an excess of the acid, relative to 1 mole ofcompound (IV), which may suitably be changed depending upon the reactionconditions.

[0087] The reaction may involve the use of a solvent inert thereto.

[0088] After completion of the reaction, for example, the reactionmixture is filtered, and the filtrate is poured into water, which isneutralized and then extracted with an organic solvent, and the organiclayer is concentrated to give a desired compound. The product may bepurified by chromatography, recrystallization, or any other technique.

[0089] Compound (II) can be produced according to the process known inthe art.

[0090] Compound (III) can be produced by the process as shown below.

[0091] wherein X, A, R², and R³ are as defined above.

[0092] First step: The step of producing compound (XV) from compound(XIII) and compound (XIV).

[0093] Compound (XV) can be produced by reacting compound (XIII) withcompound (XIV) in the presence of a base in a solvent.

[0094] Second step: The step of producing compound (XVI) from compound(XV).

[0095] Compound (XVI) can be produced by reducing compound (XV) (e.g.,by a technique such as iron reduction (Fe/acetic acid) or hydrogenation(Pd-C/H₂)).

[0096] Third step: The step of producing compound (XVII) from compound(XVI).

[0097] Compound (XVII) can be produced by reacting compound (XVI) with adiazotizing agent (e.g., nitrous acid (prepared from nitrites such assodium nitrite, and protonic acids such as acetic acid and hydrochloricacid), nitrite esters such as isoamyl nitrite and t-butyl nitrite),followed by reaction with acetic anhydride.

[0098] Fourth step: The step of producing compound (III) from compound(XVII).

[0099] Compound (III) can be produced by selective hydrolysis ofcompound (XVII).

[0100] Compound (XXV) can be produced according to the process describedin Reference Production Example 8 or 9.

[0101] For compounds (XX), (XXI), (XXVI), and (XIV), there can be usedcommercially available compounds.

[0102] The present invention will hereinafter be further illustrated bysome specific examples; however, the present invention is not limitedonly to these examples.

[0103] The following will describe production examples for the compoundsof formula (I), which are designated by their compound numbers shownbelow in Tables 1 to 3.

[0104] Production Example 1: Production of Compound a-5

[0105] To a mixture of 0.93 g of methyl[2-{2-chloro-4-fluoro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate, 0.31 g of potassium carbonate, and 10ml of N,N-dimethylformamide was added 0.58 g of methyl iodide, and themixture was stirred at room temperature for 2 hours. Then 50 ml ofdiluted hydrochloric acid was added, and the mixture was extracted withethyl acetate. The organic layer was washed with water, saturatedaqueous sodium chloride solution, dried over anhydrous sodium sulfate,and then concentrated under reduced pressure. The residue was subjectedto silica gel column chromatography to give 0.82 g of methyl[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate (compound a-5).

[0106]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 3.49-3.50 (m, 3H), 3.73 (s, 3H),4.66 (s, 2H), 6.28 (s, 1H), 6.76 (d, 1H, J=6.6 Hz), 6.9-7.2 (m, 4H),7.36 (d, 1H, J=8.9 Hz).

[0107] Production Example 2: Production of Compound a-6

[0108] To a mixture of 0.10 g of methyl[3-{2-chloro-4-fluoro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetate, 1 ml of acetonitrile, and 31 mgof potassium carbonate was added 32 mg of methyl iodide, and the mixturewas stirred at room temperature for 1.5 hours. Then, 64 mg of methyliodide was added, and the mixture was stirred at 50° C. for 1 hour. Themixture was filtered, and the filtrate was concentrated under reducedpressure. The residue was subjected to silica gel column chromatographyto give 97 mg of methyl[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetate (compound a-6).

[0109] Production Example 3: Production of Compound a-5

[0110] A mixture of 11.02 g of isoamyl nitrite and 45 ml of acetonitrilewas added dropwise to a mixture of 15.16 g of methyl[2-{2-amino-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate, 6.21 g of copper (I)chloride, 12.65 g of copper (II) chloride, and 250 ml of acetonitrile atroom temperature, and the mixture was stirred for 2 hours. The reactionmixture was poured into 2% hydrochloric acid, and the mixture wasextracted with ethyl acetate. The organic layer was washed withsaturated aqueous sodium chloride solution, dried over anhydrousmagnesium sulfate, and then concentrated. The residue was subjected tosilica gel column chromatography to give 13 g of methyl[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate (compound a-5).

[0111] Production Example 4: Production of Compound a-6

[0112] First, 88 mg of isoamyl nitrite was added dropwise to a mixtureof 0.24 g of methyl[3-{2-amino-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetate, 99 mg of copper (I)chloride, 0.20 g of copper (II) chloride, and 2.5 ml of acetonitrile atroom temperature, and the mixture was stirred for 1 hour. The reactionmixture was poured into 2% hydrochloric acid, and the mixture wasextracted with ethyl acetate. The organic layer was washed withsaturated aqueous sodium chloride solution, dried over anhydrousmagnesium sulfate, and then concentrated. The residue was subjected tosilica gel column chromatography to give 0.21 g of methyl[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetate (compound a-6).

[0113] m.p.: 52.2° C.;

[0114]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 3.50 (q, 3H, J=1.0 Hz), 3.70 (s,3H), 4.90.(d, 1H, J=15.8 Hz), 4.97 (d, 1H, J=15.8 Hz), 6.29 (s, 1H),6.9-7.0 (m, 2H), 7.32 (dd, 1H, J=7.7, 1.9 Hz), 7.37 (d, 1H, J=8.7 Hz),7.92 (dd, 1H, J=4.9, 1.9 Hz).

[0115] Production Example 5: Production of Compound b-6

[0116] First, 18 mg of isoamyl nitrite was added dropwise to a mixtureof 0.16 g of methyl2-[3-{2-amino-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]propionate, 63 mg of copper(I) chloride, 129 mg of copper (II) chloride, and 1.5 ml of acetonitrileat 0° C., and the mixture was stirred for 1 hour and further stirred atroom temperature for 1 hour. The reaction mixture was poured into amixture of 1N hydrochloric acid and ice, and the mixture was extractedwith ethyl acetate. The organic layer was washed with saturated aqueoussodium chloride solution, dried over anhydrous magnesium sulfate, andthen concentrated. The residue was subjected to silica gel columnchromatography to give 0.12 g of methyl2-[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]propionate (compound b-6) as amixture of diastereoisomers.

[0117]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 1.51 (d, 3/2H, J=7.0 Hz), 1.52 (d,3/2H, J=7.0 Hz), 3.50 (s, 3H), 3.67 (s, 3H), 5.29 (q, 1/2H, J=7.0 Hz),5.30 (q, 1/2H, J=7.0 Hz), 6.28 (s, 1/2H), 6.29 (s, 1/2H), 6.8-7.0 (m,2H), 7.3-7.4 (m, 2H), 7.8-7.9 (m, 1H).

[0118] Production Example 6: Production of Compound b-10

[0119] A solution of 10.99 g of isoamyl nitrite in 10 ml of acetonitrilewas added to a mixture of 15.46 g of ethyl2-[3-{2-amino-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]propionate, 6.19 g of copper(I) chloride, 12.61 g of copper (II) chloride, and 120 ml ofacetonitrile at room temperature, and the mixture was stirred for 3hours. The reaction mixture was poured into a mixture of ice andhydrochloric acid, and the mixture was extracted with ethyl acetate. Theorganic layer was washed with saturated aqueous sodium chloridesolution, dried over anhydrous magnesium sulfate, and then concentrated.The residue was subjected to silica gel column chromatography to give13.16 g of ethyl2-[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]propionate (compoundb-10).

[0120] Production Example 7: Production of Compound a-8

[0121] First, 92 mg of isoamyl nitrite was added dropwise to a mixtureof 0.26 g of methyl[3-{2-amino-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrah ydropyrimidin-1-yl]phenoxy}-2-pyridylthio]acetate, 0.10 g ofcopper (I) chloride, 0.21 g of copper (II) chloride, and 2.5 ml ofacetonitrile at room temperature, and the mixture was stirred for 1hour. The reaction mixture was poured into 2% hydrochloric acid, and themixture was extracted with ethyl acetate. The organic layer was washedwith saturated aqueous sodium chloride solution, dried over anhydrousmagnesium sulfate, and then concentrated. The residue was subjected tosilica gel column chromatography to give 0.10 g of methyl[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridylthio]acetate (compound a-8).

[0122]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 3.54 (s, 3H), 3.75 (s, 3H), 4.01(s, 2H), 6.33 (s, 1H), 6.9-7.0 (m, 3H), 7.42 (d, 1H, J=9.0 Hz), 8.20(dd, 1H, J=4.1, 2.2 Hz).

[0123] Production Example 8: Production of Compound a-108

[0124] First, isoamyl nitrite is added dropwise to a mixture of methyl[3-{2-amino-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-6-chloro-2-pyridyloxy]acetate, copper (I)chloride, copper (II) chloride, and acetonitrile at room temperature,and the mixture is stirred for 1 hour. The reaction mixture is pouredinto 2% hydrochloric acid, and the mixture is extracted with ethylacetate. The organic layer is washed with saturated aqueous sodiumchloride solution, dried over anhydrous magnesium sulfate, and thenconcentrated. The residue is subjected to silica gel columnchromatography to give methyl[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-6-chloro-2-pyridyloxy]acetate (compounda-108).

[0125] Production Example 9: Production of Compound a-118

[0126] First, isoamyl nitrite is added dropwise to a mixture of methyl[3-{2-amino-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrah ydropyrimidin-1-yl]phenoxy}-6-methoxy-2-pyridyloxy]acetate,copper (I) chloride, copper (II) chloride, and acetonitrile at roomtemperature, and the mixture is stirred for 1 hour. The reaction mixtureis poured into 2% hydrochloric acid, and the mixture is extracted withethyl acetate. The organic layer is washed with saturated aqueous sodiumchloride solution, dried over anhydrous magnesium sulfate, and thenconcentrated. The residue is subjected to silica gel columnchromatography to give methyl[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-6-methoxy-2-pyridyloxy]acetate (compounda-118).

[0127] Production Example. 10: Production of Compound b-5

[0128] First, 0.23 g of2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol was dissolved in 6 ml ofN,N-dimethylformamide, to which 0.22 g of potassium carbonate was addedand 0.13 g of methyl 2-bromopropionate was added under stirring at roomtemperature, and the mixture was stirred at 80° C. for 3 hours. Thereaction mixture was cooled to room temperature and then poured into icewater, and the mixture was extracted with ethyl acetate. The organiclayer was washed with saturated aqueous sodium chloride solution, driedover anhydrous magnesium sulfate, and then concentrated. The residue wassubjected to silica gel column chromatography to give 0.23 g of methyl2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate (compound b-5).

[0129]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 1.47 (d, 3H, J=6.8 Hz), 3.50 (q,3H, J=0.7 Hz), 3.6-3.8 (m, 3H), 4.6-4.8 (m, 1H), 6.28 (s, 1H), 6.7-6.8(m, 1H), 6.8-6.9 (m, 1H), 6.9-7.1 (m, 1H), 7.1-7.2 (m, 2H), 7.3-7.4 (m,1H).

[0130] Production Example 11: Production of Compound a-121

[0131] First, 0.20 g of2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenol was dissolved in 2 ml ofN,N-dimethylformamide, to which 0.083 g of potassium carbonate wasadded, and the mixture was stirred at room temperature for 50 minutes.Then, 0.077 g of t-butyl chloroacetate was added, and the mixture wasstirred at 40° C. to 60° C. for 2 hours. After left for cooling, icewater was poured into the reaction mixture, and after addition of ethylacetate and saturated aqueous sodium chloride solution, the mixture wassubjected to phase separation. The organic layer was washed withsaturated aqueous sodium chloride solution, dried over magnesiumsulfate, and then concentrated. The residue was subjected to silica gelcolumn chromatography (eluent: n-hexane/ethyl acetate=6/1) to give 10.39g of t-butyl[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate (compound a-121).

[0132]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 1.44 (s, 9H), 3.49 (d, 3H, J=1.1Hz), 4.53 (s, 2H), 6.27 (s, 1H), 6.80 (d, 1H, J=6.6 Hz), 6.8-7.2 (m,4H), 7.35 (d, 1H, J=8.9 Hz);

[0133] m.p.: 55.6° C.

[0134] The physical properties of compounds produced by the same processas described in Production Examples 10 and 11 are shown below.

[0135] Ethyl2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate (compound b-9)

[0136]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 1.23 (t, 3H, J=7.1 Hz), 1.47 (d,3H, J=6.8 Hz), 3.50 (s, 3H), 4.1-4.3 (m, 2H), 4.6-4.8 (m, 1H), 6.3-6.4(m, 1H), 6.7-7.0 (m, 3H), 7.0-7.2 (m, 2H), 7.3-7.4 (m, 1H).

[0137] Ethyl[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate (compound a-9)

[0138]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 1.26 (t, 3H, J=7.1 Hz), 3.50 (s,3H), 4.19 (q, 2H, J=7.2 Hz), 4.64 (s, 2H), 6.28 (s, 1H), 6.7-6.8 (m,1H), 6.9-7.2 (m, 4H), 7.36 (d, 1H, J=8.8 Hz).

[0139] Production Example 12: Production of Compound a-28

[0140] A mixture of 0.30 g of methyl[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetate (compound a-6), 0.06 gof sodium carbonate, and 3.0 ml of cyclopentanol was stirred at 100° C.for 1.5 hours and then at 120° C. for 2 hours. The reaction mixture wascooled to room temperature and then poured into water, and the mixturewas extracted with ethyl acetate. The organic layer was washed withsaturated aqueous sodium chloride solution, dried over anhydrousmagnesium sulfate, and then concentrated. The residue was subjected tosilica gel column chromatography to give 0.15 g of cyclopentyl[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetate (compound a-28).

[0141] Production Example 13: Production of Compound a-10

[0142] A mixture of 0.60 g of methyl[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetate (compound a-6), 0.13 gof sodium carbonate, and 7.0 ml of ethanol was heated at reflux for 2hours. After cooling to room temperature, the solvent was distilled outunder reduced pressure, and the residue was subjected to silica gelchromatography to give 0.55 g of ethyl[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetate (compound a-10).

[0143]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 1.25 (t, 3H, J=7.1. Hz), 3.50 (q,3H, J=1.2 Hz), 4.16 (q, 2H, J=7.1 Hz), 4.88 (d, 1H, J=15.9 Hz), 4.96 (d,1H, J=15.9 Hz), 6.29 (s, 1H), 6.9-7.0 (m, 2H), 7.3-7.4 (m, 2H), 7.9-8.0(m, 1H).

[0144] Production Example 14: Production of Compound a-14

[0145] A mixture of 0.60 g of methyl[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetate (compound a-6), 0.13 gof sodium carbonate, and 7.0 ml of n-propanol was stirred under refluxfor 2 hours. After cooling to room temperature, the solvent wasdistilled out under reduced pressure, and the residue was subjected tosilica gel column chromatography to give propyl[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetate (compound a-14).

[0146]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 0.89 (t, 3H, J=7.3 Hz), 1.63 (qt,2H, J=7.3, 6.5 Hz), 3.50 (q, 3H, J=0.8 Hz), 4.06 (t, 2H, J=6.5 Hz), 4.89(d, 1H, J=16.0 Hz), 4.97 (d, 1H, J=16.0 Hz), 6.28 (s, 1H), 6.91 (dd, 1H,J=7.8, 5.0 Hz), 6.93 (d, 1H, J=6.5 Hz), 7.31 (dd, 1H, J=7.8, 1.6 Hz),7.36 (d, 1H, J=8.9 Hz), 7.91 (dd, 1H, J=5.0, 1.6 Hz).

[0147] Production Example 15: Production of Compound a-20

[0148] A mixture of 0.30 g of methyl[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetate (compound a-6), 0.06 gof sodium carbonate, and 3.0 ml of n-pentanol was stirred at 100° C. for1.5 hours. After cooling to room temperature, the reaction mixture waspoured into water, and the mixture was extracted with ethyl acetate. Theorganic layer was washed with saturated aqueous sodium chloridesolution, dried over anhydrous magnesium sulfate, and then concentrated.The residue was subjected to silica gel column chromatography to give0.07 g of pentyl[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetate (compound a-20).

[0149]¹H-NMR (CDCl₃, 300 MHz) δ(ppm) 0.88 (t, 3H, J=6.6 Hz), 1.2-1.4 (m,4H), 1.5-1.7 (m, 2H), 3.50 (q, 3H, J=1.0 Hz), 4.0-4.2 (m, 2H), 4.8-5.1(m, 2H), 6.29 (s, 1H), 6.9-7.0 (m, 2H), 7.28 (dd, 1H, J=7.9, 1.4 Hz),7.37 (d, 1H, J=9.0 Hz), 7.91 (dd, 1H, J=4.9, 1.4 Hz).

[0150] Production Example 16: Production of Compound b-19

[0151] First,2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetra hydropyrimidin-1-yl]phenoxy}phenoxy]propionic acid (compoundb-1) is dissolved in tetrahydrofuran, to which thionyl chloride is addedunder stirring, and the mixture is heated and stirred under reflux.After left for cooling and the subsequent concentration, the residue isdissolved in tetrahydrofuran (hereinafter referred to as solution A).Tetrahydrofuran is added to 1-pentyl alcohol, to which solution A idadded and pyridine is then added. After stirring at room temperature, 2%aqueous hydrochloric acid is added to the reaction mixture, and themixture is extracted with ethyl acetate. The organic layer is washedwith saturated aqueous sodium chloride solution, dried over magnesiumsulfate, and then concentrated. The residue is subjected to silica gelcolumn chromatography (eluent: hexane/ethyl acetate=5/1) to give pentyl2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate (compound b-19).

[0152] Production Example 17: Production of Compound a-21

[0153] First, 1.0 g of[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetic acid (compound a-1) wasdissolved in tetrahydrofuran, to which 0.7 ml of thionyl chloride wasadded under stirring, and the mixture was heated and stirred underreflux for 2 hours. After left for cooling and the subsequentconcentration, the residue was dissolved in 3 ml of tetrahydrofuran(hereinafter referred to as solution B). Then, 0.7 ml of tetrahydrofuranwas added to 0.05 g of allyl alcohol, to which a third part of solutionB was added and 0.17 ml of pyridine was then added. After stirring atroom temperature for 2 hours, 2% aqueous hydrochloric acid was pouredinto the reaction mixture, and the mixture was extracted with ethylacetate. The organic layer was washed with saturated aqueous sodiumchloride solution, dried over magnesium sulfate, and then concentrated.The residue was subjected to silica gel column chromatography (eluent:hexane/ethyl acetate=5/1) to give 0.08 g of allyl[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate (compound a-21).

[0154]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 3.50 (d, 3H, J=1.2 Hz), 4.62-4.64(m, 2H), 4.68 (s, 2H), 5.22-5.32 (m, 2H), 5.8-6.0 (m, 1H), 6.28 (s, 1H),6.76 (d, 1H, J=6.5 Hz), 6.91-7.14 (m, 4H), 7.35 (d, 1H, J=8.6 Hz).

[0155] Production Example 18: Production of Compound a-123

[0156] First, 1.5 g of[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetic acid (compound a-1) wasdissolved in 6 ml, to which 1 ml of thionyl chloride was added understirring, and the mixture was heated and stirred under reflux for 2hours and 10 minutes. After left for cooling and the subsequentconcentration, the residue was dissolved in 3 ml of tetrahydrofuran(hereinafter referred to as solution C). Then, 1 ml of tetrahydrofuranwas added to 0.273 g of isobutyl alcohol, to which a third part ofsolution C was added and 0.25 ml of pyridine was then added. Afterstirring at room temperature for 2 hours, 2% aqueous hydrochloric acidwas poured into the reaction mixture, to which ethyl acetate was added,and the mixture was subjected to phase separation. The organic layer waswashed with saturated aqueous sodium chloride solution, dried overmagnesium sulfate, and then concentrated. The residue was subjected tosilica gel column chromatography (eluent: hexane/ethyl acetate=6/1) togive 0.34 g of isobutyl[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate (compound a-123).

[0157]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 0.89 (d, 6H, J=6.7 Hz), 1.8-2.0(m, 1H), 3.50 (d, 3H, J=1.2 Hz), 3.92 (d, 2H, J=6.7 Hz), 4.67 (s, 2H),6.28 (s, 1H), 6.77 (d, 1H, J=6.6 Hz), 6.85-7.15 (m, 4H), 7.36 (d, 1H,J=8.9 Hz).

[0158] Production Example 19: Production of Compound a-104

[0159] First, 0.13 g of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimidehydrochloride was added to a mixture of 0.30 g of[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifuoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetic acid (compound a-2), 56mg of o-methylhydroxylamine, 68 mg of triethylamine, and 2 ml ofN,N-dimethylformamide at room temperature, and the mixture was stirredfor 2 hours. The mixture was poured into water, and the mixture wasextracted with ethyl acetate. The organic layer was dried over anhydrousmagnesium sulfate and then concentrated. The residue was subjected tosilica gel column chromatography to give 90 mg ofN-methoxy-[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetamide (compounda-104).

[0160]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 3.52 (s, 3H), 3.74 (s, 3H), 4.87(s, 2H), 6.32 (s, 1H), 6.71 (d, 1H, J=6.0 Hz), 6.99 (dd, 1H, J=7.6, 5.0Hz), 7.38 (dd, 1H, J=7.6, 1.7 Hz), 7.44 (d, 1H, J=8.7 Hz), 8.00 (dd, 1H,J=5.0, 1.7 Hz), 8.7-9.0 (bs, 1H).

[0161] Production Example 20: Production of Compound a-32

[0162] First, 0.13 g of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimidehydrochloride was added to a mixture of 0.30 g of[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetic acid (compound a-2), 60mg of methyl glycolate, and 2 ml of N,N-dimethylformamide at roomtemperature, and the mixture was stirred for 1.5 hours. The mixture waspoured into water, and the mixture was extracted with ethyl acetate. Theorganic layer was dried over anhydrous magnesium sulfate and thenconcentrated. The residue was subjected to silica gel columnchromatography to give 0.18 g of methyl[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetoxyacetate (compound a-32).

[0163]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 3.50 (s, 3H), 3.74 (s, 3H), 4.65(s, 2H), 5.01 (d, 1H, J=16.2 Hz), 5.09 (d, 1H, J=16.2 Hz), 6.28 (s, 1H),6.88 (d, 1H, J=6.7 Hz), 6.93 (dd, 1H, J=7.8, 4.9 Hz), 7.32 (dd, 1H,J=7.8, 1.4 Hz), 7.37 (d, 1H, J=9.0 Hz), 7.93 (dd, 1H, J=4.9, 1.4 Hz).

[0164] Production Example 21: Production of Compound a-98

[0165] First, 0.13 g of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimidehydrochloride was added to a mixture of 0.30 g of[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetic acid (compound a-2), 49mg of acetone oxime, and 2 ml of N,N-dimethylformamide at roomtemperature, and the mixture was stirred for 2 hours. The mixture waspoured into water, and the mixture was extracted with ethyl acetate. Theorganic layer was dried over anhydrous magnesium sulfate and thenconcentrated. The residue was subjected to silica gel columnchromatography to give 0.16 g of acetoneO-[3-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-pyridyloxy]acetyloxime (compound a-98).

[0166]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 1.94 (s, 3H), 2.01 (s, 3H), 3.49(s, 3H), 5.0-5.2 (m, 2H), 6.27 (s, 1H), 6.92 (dd, 1H, J=7.8, 4.9 Hz),6.98 (d, 1H, J=6.5 Hz), 7.3-7.4 (m, 2H), 7.92 (d, 1H, J=4.9 Hz).

[0167] The following will describe production examples for intermediatesin the production of compounds (I).

[0168] Reference Production Example 1

[0169] Step 1:

[0170] A mixture of 4.05 g of 2-benzyloxyphenol and 9.5 ml ofN,N-dimethylformamide was added dropwise to a mixture of 0.80 g ofsodium hydride and 20 ml of N,N-dimethylformamide under ice cooling, andthe mixture was stirred for 30 minutes. A mixture of 7.1 g of2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene and 17 ml of N,N-dimethylformamide was addeddropwise at the same temperature, and the mixture was stirred for 1hour. The reaction mixture was poured into ice water, and the mixturewas extracted with ethyl acetate. The organic layer was washed once with1N hydrochloric acid and once with saturated aqueous sodium chloridesolution, dried over anhydrous magnesium sulfate, and then concentrated.The residue was subjected to silica gel column chromatography to give8.6 g of2-(2-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene.

[0171]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 3.52 (q, 3H, J=1.1 Hz), 5.01 (s,2H), 6.31 (s, 1H), 6.81 (d, 1H, J=6.0 Hz), 6.9-7.1 (m, 2H), 7.1-7.4 (m,7H), 7.78 (d, 1H, J=8.7 Hz).

[0172] Step 2:

[0173] To a mixture of 8.6 g of iron powder, 27 ml of acetic acid, and2.7 ml of water was added dropwise a solution of 8.6 g of2-(2-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene in 23 ml of acetic acid,while the temperature of the reaction mixture was kept at 35° C. orlower. After completion of the dropwise addition, the reaction mixturewas stirred for 2 hours and then filtered through Celite. The filtratewas diluted with ethyl acetate. The mixture was neutralized withsaturated aqueous sodium bicarbonate solution. The organic layer waswashed with saturated aqueous sodium chloride solution, dried overanhydrous magnesium sulfate, and then concentrated. The residue wassubjected to silica gel column chromatography to give 6.46 g of2-(2-benzyloxyphenoxy)-5-fluoro4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]aniline.

[0174]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 3.50 (q, 3H, J=1.2 Hz), 5.06 (s,2H), 6.29 (s, 1H), 6.57 (dd, 1H, J=8.5, 1.6 Hz), 6.9-7.0 (m, 1H),7.0-7.1 (m, 3H), 7.2-7.4 (m, 6H).

[0175] Step 3:

[0176] First, 4.46 g of isoamyl nitrite was added dropwise to a mixtureof 6.46 g of 2-(2-benzyloxyphenoxy)-5-fluoro-4-[3-methyl-2, 6,-dioxo-4-(trifluoromethyl)-1, 2,3,6-tetrahydropyrimidin-1-yl]aniline,2.45 g of copper (I) chloride, 5.04 g of copper (II) chloride, and 90 mlof acetonitrile at room temperature, and the mixture was stirred for 1hour. The reaction mixture was poured into 2% hydrochloric acid, and themixture was extracted with ethyl acetate. The organic layer was washedwith saturated aqueous sodium chloride solution, dried over anhydrousmagnesium sulfate, and then concentrated. The residue was subjected tosilica gel column chromatography to give 4.6 g of([2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]methyl)benzene.

[0177] m.p.: 50.8° C.

[0178] Step 4:

[0179] To 4.5 g of([2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]methyl)benzene were added 230 ml ofethyl acetate and 0.46 g of 10% palladium/carbon, and the mixture wasstirred at room temperature under an atmosphere of hydrogen gas for 5hours. The gas in the atmosphere on the reaction system was replacedwith nitrogen gas, and the reaction mixture was filtered through Celite.The filtrate was concentrated to give 3.57 g of2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahy dropyrimidin-1-yl]phenoxy}phenol.

[0180] m.p.: 55.4° C.

[0181] Reference Production Example 2

[0182] First, 0.365 g of methyl2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionate was dissolved in 4 ml of1,4-dioxane, to which a mixed solution of 1 ml of concentratedhydrochloric acid and 1 ml of water was added under stirring, and themixture was heated and stirred under reflux for 5 hours and 45 minutes.The reaction mixture was then left for cooling, into which ice water waspoured, and after addition of ethyl acetate and saturated aqueous sodiumchloride solution, the mixture was subjected to phase separation. To theorganic layer was added aqueous sodium hydrogencarbonate solution, andthe mixture was subjected to phase separation. To the aqueous layer wasadded aqueous hydrochloric acid solution for acidification, to whichethyl acetate was added, and the mixture was subjected to phaseseparation. The organic layer was washed with saturated aqueous sodiumchloride solution, dried over magnesium sulfate, and then concentratedto give 0.183 g of2-[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]propionic acid.

[0183]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 1.53 (d, 3H, J=6.9 Hz), 3.51 (s,3H), 4.76-4.83 (m, 1H), 6.32 (d, 1H, J=3.5 Hz), 6.63-6.67 (m, 1H),7.0-7.1 (m, 2H), 7.1-7.2 (m, 2H), 7.38 (d, 1H, J=9.0 Hz).

[0184] Reference Production Example 3

[0185] First, 0.4 g of methyl.[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate was dissolved in 4 ml of1,4-dioxane, to which a mixed solution of 1 ml of concentratedhydrochloric acid and 1 ml of water was added under stirring, and themixture was heated and stirred under reflux for 12 hours. The reactionmixture was then left for cooling, into which ice water was poured, andafter addition of ethyl acetate and saturated aqueous sodium chloridesolution, the mixture was subjected to phase separation. To the organiclayer was added aqueous sodium hydrogencarbonate solution, and themixture was subjected to phase separation. To the aqueous layer wasadded aqueous hydrochloric acid solution for acidification, to whichethyl acetate was added, and the mixture was subjected to phaseseparation. The organic layer was washed with saturated aqueous sodiumchloride solution, dried over magnesium sulfate, and then concentratedto give 0.252 g of[2-{2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetic acid.

[0186]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 3.50 (d, 3H, J=1.2 Hz), 4.66 (s,2H), 6.31 (s, 1H), 6.69 (d, 1H, J=6.5 Hz), 6.98-7.20 (m, 4H), 7.38 (d,1H, J=8.8 Hz).

[0187] Reference Production Example 4

[0188] Step 1:

[0189] First, 2.73 g of 2-methoxyphenol and 5.5 g of potassium carbonatewere added to 20 ml of N,N-dimethylformamide, and the temperature wasincreased to 60° C. To the mixture was added dropwise a solutionconsisting of 4.3 g of N-(2,5-difluoro-4-nitrophenyl)acetamide and 30 mlof N,N-dimethylformamide at a temperature of 60° C. to 65° C. Afterstirring while keeping the temperature for 1 hour, the mixture wascooled to room temperature and then poured into water, and the mixturewas extracted with ethyl acetate. The organic layer was washed withdiluted hydrochloric acid and water, dried over magnesium sulfate, andthen concentrated to give 5.52 g ofN-[2-fluoro-5-(2-methoxyphenoxy)-4-nitrophenyl]acetamide.

[0190]¹H-NMR (250 MHz, CDCl₃) δ(ppm): 2.16 (3H, s), 3.78 (3H, s),6.85-7.22 (4H, m), 7.75-7.83 (1H, br), 7.83 (1H, d, J=10.7 Hz), 8.04(1H, d, J=6.9 Hz).

[0191] Step 2:

[0192] First, 5.4 g ofN-[2-fluoro-5-(2-methoxyphenoxy)-4-nitrophenyl]acetamide was dissolvedin 50 ml of methylene chloride, to which 4.7 g of boron tribromide wasadded under ice cooling. After stirring at the same temperature for 2hours, concentrated hydrochloric acid was added, and the mixture waspoured into water, and the mixture was extracted with ethyl acetate. Theorganic layer was washed with water, dried over magnesium sulfate, andthen concentrated. The resulting crystals were washed with t-butylmethyl ether to give 3.2 g ofN-[2-fluoro-5-(2-hydroxyphenoxy)-4-nitrophenyl]acetamide.

[0193]¹H-NMR (300 MHz, CDCl₃) δ(ppm): 2.20 (3H, s), 6.33 (1H, bs),6.86-7.23 (4H, m), 7.63 (1H, bs), 7.81 (1H, d, J=10.3 Hz), 8.34 (1H, d,J=6.7 Hz).

[0194] Step 3:

[0195] First, 3.02 g ofN-[2-fluoro-5-(2-hydroxyphenoxy)-4-nitrophenyl]acetamide was dissolvedin 20 ml of N,N-dimethylformamide, to which 1.5 g of potassium carbonatewas added, and the mixture was stirred at room temperature for 1 hour.Then, 1.6 g of methyl bromoacetate was added at room temperature. Afterstirring at the same temperature for 2 hours, the mixture was pouredinto water, and the mixture was extracted with ethyl acetate. Theorganic layer was washed with diluted hydrochloric acid and water, driedover magnesium sulfate, and then concentrated. The resulting crystalswere washed with t-butyl methyl ether to give 3.01 g of methyl[2-(5-acetylamino-4-fluoro-2-nitrophenoxy)phenoxy]acetate.

[0196]¹H-NMR (250 MHz, CDCl₃) δ(ppm): 2.16 (3H, s), 3.73 (3H, s), 4.62(2H, s), 6.95-7.26 (4H, m), 7.71 (1H, bs), 7.85 (1H, d, J=10.7 Hz), 8.06(1H, d, J=6.9 Hz).

[0197] Step 4:

[0198] To a mixture of 40 ml of acetic acid and 40 ml of water was added2.2 g of iron powder, and the temperature was increased to 80° C. To themixture was added 3.0 g of methyl[2-(5-acetylamino-4-fluoro-2-nitrophenoxy)phenoxy]acetate, and themixture was heated at reflux for 30 minutes. The mixture was then pouredinto water, and the mixture was extracted with ethyl acetate. Theorganic layer was washed with water and saturated aqueous sodiumbicarbonate solution, dried over magnesium sulfate, and thenconcentrated to give 2.01 g of methyl[2-(5-acetylamino-2-amino-4-fluorophenoxy)phenoxy]acetate.

[0199]¹H-NMR (250 MHz, CDCl₃) δ(ppm): 2.11 (3H, s), 3.31-4.15 (2H, br),3.76 (3H, s), 4.71 (2H, s), 6.54 (1H, d, J=11.9 Hz), 6.90-7.01 (4H, m),7.17 (1H, bs), 7.69 (1H, d, J=7.5 Hz).

[0200] Step 5:

[0201] To 30 ml of concentrated hydrochloric acid was added 2.0 g ofmethyl [2-(5-acetylamino-2-amino-4-fluorophenoxy)phenoxy]acetate, andthe mixture was stirred at room temperature for 1 hour. Then, an aqueoussolution consisting of 0.42 g of sodium nitrite and 3 ml of water wasadded under ice cooling. After stirring at the same temperature for 1hour, 40 ml of t-butyl methyl ether was added and 0.85 g of copper (I)chloride was added. After stirring for 30 minutes, water was added, andthe mixture was extracted with t-butyl methyl ether. The organic layerwas washed with water, dried over magnesium sulfate, and thenconcentrated. The residue was subjected to column chromatography(eluent: hexane/ethyl acetate=2/1) to give 0.52 g of methyl[2-(5-acetylamino-2-chloro-4-fluorophenoxy)phenoxy]acetate.

[0202] m.p.: 138.9° C.

[0203] Step 6:

[0204] To 10 ml of a methanol solution of a boron trifluoride methanolcomplex was added 0.25 g of methyl[2-(5-acetylamino-2-chloro-4-fluorophenoxy)phenoxy]acetate, and themixture was heated and stirred for 3 hours. The reaction mixture wasthen concentrated. The residue was dissolved in ethyl acetate, and thesolution was washed with saturated aqueous sodium bicarbonate solution,dried over magnesium sulfate, and then concentrated to give 0.2 g ofmethyl [2-(5-amino-2-chloro-4-fluorophenoxy)phenoxy]acetate.

[0205]¹H-NMR (250 MHz, CDCl₃) δ(ppm): 3.74 (3H, s), 3.86 (2H, br), 4.70(2H, s), 6.36 (1H, d, J=8.21 Hz), 6.83-7.09 (5H, m).

[0206] Reference Production Example 5

[0207] First, 1.77 g of 2,4,5-trifluoronitrobenzene and 1.94 g of3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2, 3,6-tetrahydropyrimidinewere dissolved in 10 ml of dimethylsulfoxide, to which 1.52 g ofanhydrous potassium carbonate was added at room temperature, and themixture was stirred at 80° C. for 1 hour. The reaction mixture wascooled to room temperature and then poured into ice water, and themixture was extracted with ethyl acetate. The organic layer was washedwith saturated aqueous sodium chloride solution, dried over anhydrousmagnesium sulfate, and then concentrated. The residue was subjected tosilica gel column chromatography to give 1.51 g of2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene.

[0208] m.p.: 150° C.

[0209] Reference Production Example 6

[0210] A mixture of 15.16 g of methyl (2-hydroxyphenoxy)acetate, 29.23 gof2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene, 11.5 g of anhydrous potassium carbonate, and160 ml of N,N-dimethylformamide was stirred at room temperature for 30minutes and then at 70° C. for 3 hours. Another 5 g of methyl(2-hydroxyphenoxy)acetate was added, and the mixture was stirred for 1hour. The reaction mixture was poured into 2% aqueous hydrochloric acidsolution, and the mixture was extracted with ethyl acetate. The organiclayer was washed with saturated aqueous sodium chloride solution, driedover anhydrous magnesium sulfate, and then concentrated. The residue wassubjected to silica gel column chromatography to give 17.8 g of methyl[2-{4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-2-nitrophenoxy}phenoxy]acetate.

[0211]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 3.50 (q, 3H, J=1.0 Hz), 3.70 (s,3H), 4.63 (s, 2H), 6.28 (s, 1H), 6.88 (d, 1H, J=8.4 Hz), 6.93 (d, 1H,J=6.0 Hz), 7.0-7.1 (m, 1H), 7.1-7.3 (m, 2H), 7.87 (d, 1H, J=8.7 Hz).

[0212] Reference Production Example 7

[0213] To a mixture of 19 g of iron powder, 60 ml of acetic acid, and 6ml of water was added dropwise a solution of 19.12 g of methyl[2-{4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-2-nitrophenoxy}phenoxy]acetate in 60 ml of acetic acid underice cooling. After completion of the dropwise addition, the temperaturewas increased to room temperature, and the mixture was stirred for 4hours. The reaction mixture was filtered through Celite, and thefiltrate was diluted with ethyl acetate. The mixture was washed withwater, saturated aqueous sodium bicarbonate solution and saturatedaqueous sodium chloride solution, dried over anhydrous magnesiumsulfate, and then concentrated. The residue was subjected to silica gelchromatography to give 15.16 g of methyl[2-{2-amino-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}phenoxy]acetate.

[0214]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 3.51 (q, 3H, J=0.9 Hz), 3.76 (s,3H), 4.2-4.4 (b, 2H), 4.69 (s, 2H), 6.29 (s, 1H), 6.6-6.7 (m, 2H),6.9-7.1 (m, 4H).

[0215] Reference Production Example 8

[0216] Step 1:

[0217] A solution consisting of 4.85 g of methyl[2-(5-amino-2-chloro-4-fluorophenoxy)phenoxy]acetate, 2.88 g of ethyltrifluoroacetoacetate, and 40 ml of toluene was azeotropically distilledfor 6 hours, while passing through molecular sieves 5A to removeethanol. The reaction mixture was cooled, and 50 ml of ethyl acetate wasthen added. The organic layer was washed with concentrated hydrochloricacid, water and saturated aqueous sodium chloride solution, dried overanhydrous sodium sulfate, and then concentrated under reduced pressure.The residue was washed with hexane to give 5.82 g of crude methyl[2-(5-{3,3-dihydroxy-4,4,4-trifluorobutyryl}amino-2-chloro-4-fluorophenoxy)phenoxy]acetate.

[0218] m.p.: 165.3° C.

[0219] Step 2:

[0220] To a solution of 1.0 g of crude methyl[2-(5-{3,3-dihydroxy-4,4,4-trifluorobutyryl}amino-2-chloro-4-fluorophenoxy)_(p)henoxy]acetate and 3 ml of tetrahydrofuran were added 4 ml of aceticacid and 0.87 g of potassium cyanate, and the mixture was stirred atroom temperature for 6 hours and then heated at reflux at 120° C. for 2hours. After cooling, 30 ml of water was added, and the mixture wasextracted with ethyl acetate. The organic layer was washed withsaturated aqueous sodium bicarbonate solution, water and saturatedaqueous sodium chloride solution, dried over anhydrous sodium sulfate,and then concentrated under reduced pressure. The residue was subjectedto silica gel column chromatography to give 0.67 g of methyl[2-{2-chloro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-4-fluorophenoxy}phenoxy]acetate.

[0221]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 3.72 (3H, s), 4.65 (2H, s), 6.16(1H, s), 6.77 (1H, d, J=6.6 Hz), 6.89-7.15 (4H, m), 7.36 (1H, d, J=8.9Hz).

[0222] Reference Production Example 9

[0223] Step 1:

[0224] First, 2.08 g of potassium carbonate was added to a solution of3.0 g of 3-hydroxy-2-(methoxycarbonyl)methoxypyridine, 2.95 g ofN-(2,5-difluoro-4-nitrophenyl)acetamide, and 40 ml ofN,N-dimethylformamide. The mixture was stirred at 60° C. to 70° C. for 2hours, cooled to room temperature, and then poured into water. Themixture was extracted with ethyl acetate. The organic layer was washedwith saturated aqueous sodium chloride solution, dried over anhydrousmagnesium sulfate, and then concentrated to give crude crystals. Thecrude crystals were washed with diisopropyl ether to give 3.67 g ofN-[2-fluoro-5-{2-(methoxycarbonyl)methoxy-3-pyridyloxy}-4-nitrophenyl]acetamide.

[0225]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 2.21 (s, 3H), 3.72 (s, 3H), 4.90(s, 2H), 6.96 (dd, 1H, J=7.8, 5.0 Hz), 7.35 (dd, 1H, J=7.8, 1.6 Hz),7.5-7.6 (b, 1H), 7.90 (d, 1H, J=10.6 Hz), 7.97 (dd, 1H, J=5.0, 1.6 Hz),8.15 (d, 1H, J=6.8 Hz).

[0226] Step 2:

[0227] To a mixture of 3.6 g of iron powder, 10 ml of acetic acid, and 1ml of water was added dropwise a solution of 3.67 g ofN-[2-fluoro-5-{2-(methoxycarbonyl)methoxy}-3-pyridyloxy]-4-nitrophenyl]acetamide, 12 ml of acetic acid, and 2 ml of ethyl acetate, while thetemperature of the reaction mixture was kept at 45° C. or lower. Aftercompletion of the dropwise addition, the reaction mixture was stirred at40° C. for 1 hour. The reaction mixture was then filtered throughCelite, and the filtrate was concentrated. The residue was diluted withsaturated aqueous sodium bicarbonate solution, and the mixture wasextracted with ethyl acetate. The organic layer was washed withsaturated aqueous sodium bicarbonate solution, dried over anhydrousmagnesium sulfate, and then concentrated. The residue was washed withdiisopropyl ether to give 3.09 g ofN-[4-amino-2-fluoro-5-{2-(methoxycarbonyl)methoxy-3-pyridyloxy}phenyl]acetamide.

[0228]¹H-NMR(CDCl₃, 250 MHz) δ(ppm): 2.15 (s, 3H), 3.77 (s, 3H), 3.9-4.1(b, 2H), 5.03 (s, 2H), 6.56 (d, 1H, J=11.8 Hz), 6.84 (dd, 1H, J=7.9, 5.0Hz), 7.0-7.2 (b, 1H), 7.14 (dd, 1H, J=7.9, 1.5 Hz), 7.80 (dd, 1H, J=5.0,1.5 Hz), 7.84 (d, 1H, J=7.6 Hz).

[0229] Step 3:

[0230] A solution of 2.01 g of isoamyl nitrite in 1 ml of acetonitrilewas added dropwise to a mixture of 2.0 g ofN-[4-amino-2-fluoro-5-{2-(methoxycarbonyl)methoxy-3-pyridyloxy}phenyl]acetamide, 1.13 g of copper (I) chloride, 2.31 g of copper (II) chloride,and 20 ml of acetonitrile at room temperature, and the mixture wasstirred for 1 hour. The reaction mixture was poured into 2% hydrochloricacid, and the mixture was extracted with ethyl acetate. The organiclayer was washed with saturated aqueous sodium chloride solution, driedover anhydrous magnesium sulfate, and then concentrated. The residue wassubjected to silica gel column chromatography to give 1.04 g ofN-[4-chloro-2-fluoro-5-{2-(methoxycarbonyl)methoxy-3-pyridyloxy}phenyl]acetamide.

[0231]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 2.18 (s, 3H), 3.75 (s, 3H), 4.98(s, 2H), 6.87 (dd, 1H, J=7.8, 4.9 Hz), 7.08 (dd, 1H, J=7.8, 1.4 Hz),7.23 (d, 1H, J=10.3 Hz), 7.3-7.4 (b, 1H), 7.86 (dd, 1H, J=4.9, 1.4 Hz)8.07 (d, 1H, J=7.3 Hz).

[0232] Step 4:

[0233] First, 20 ml of a methanol solution of a boron trifluoridemethanol complex was mixed with 1.04 g ofN-[4-chloro-2-fluoro-5-{2-(methoxycarbonyl)methoxy-3-pyridyloxy}phenyl]acetamide, and the mixture was stirred at 60° C. to 70° C. for 3 hours andthen concentrated. The residue was diluted with saturated aqueous sodiumbicarbonate solution, and the mixture was extracted with ethyl acetate.The organic layer was washed with saturated aqueous sodium chloridesolution, dried over anhydrous magnesium sulfate, and then concentrated.The residue was subjected to column chromatography to give 0.87 g of4-chloro-2-fluoro-5-{2-(methoxycarbonyl)methoxy-3-pyridyloxy}aniline.

[0234]¹H-NMR (CDCl₃, 250 MHz) δ(ppm) 3.77 (s, 3H), 3.7-3.9 (b, 2H), 5.00(s, 2H), 6.49 (d, 1H, J=8.2 Hz), 6.88 (dd, 1H, J=7.9, 5.0 Hz), 7.08 (d,1H, J=10.3 Hz), 7.10 (dd, 1H, J=7.9, 1.6 Hz), 7.87 (dd, 1H, J=5.0, 1.6Hz).

[0235] Step 5:

[0236] A mixture of 0.5 g of4-chloro-2-fluoro-5-{2-(methoxycarbonyl)methoxy-3-pyridyloxy}aniline,0.28 g of ethyl trifluoroacetoacetate, and 10 ml of toluene wasazeotropically distilled for 3 hours, while passing through molecularsieves 5A to remove ethanol. After cooling, the reaction mixture wasconcentrated to give 0.71 g ofN-[4-chloro-2-fluoro-5-{2-(methoxycarbonyl)methoxy-3-pyridyloxy}phenyl]trifluoroacetoacetamide.

[0237] m.p.: 158.8° C.

[0238] Step 6:

[0239] To a mixture of 0.71 g ofN-[4-chloro-2-fluoro-5-{2-(methoxycarbonyl)methoxy-3-pyridyloxy}phenyl]trifluoroacetoacetamide and 2 ml of acetic acid was added sodium cyanate,and the mixture was stirred at 50° C. for 1 hour and then at 110° C. for1.5 hours. After cooling, water was poured into the reaction mixture,and the mixture was extracted with ethyl acetate. The organic layer waswashed with saturated aqueous sodium bicarbonate solution, saturatedaqueous sodium chloride solution, dried over anhydrous magnesiumsulfate, and then concentrated. The residue was subjected to silica gelcolumn chromatography to give 0.30 g of3-{2-chloro-4-fluoro-5-[2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyridin-1-yl]phenoxy}-2-(methoxycarbonyl) methoxypyridine.

[0240]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 3.70 (s, 3H), 4.93 (s, 2/2H), 4.94(s, 2/2H), 6.19(s, 1H), 6.9-7.0 (m, 2H), 7.3-7.4 (m, 1H), 7.38 (d, 1H,J=8.9 Hz), 7.93 (dd, 1H, J=4.9, 1.6 Hz);

[0241] m.p.: 75.3° C.

[0242] Reference Production Example 10

[0243] Step 1:

[0244] First, 0.4 g of sodium hydride was added to a mixture of 1.59 gof 2-chloro-3-nitropyridine, 0.95 g of methyl glycolate, and 10 ml of1,4-dioxane at 10° C. After stirring at room temperature for 2 hours,the reaction mixture was poured into ice water, and the mixture wasextracted with ethyl acetate. The organic layer was dried over anhydrousmagnesium sulfate and then concentrated. The residue was subjected tosilica gel column chromatography to give 1.5 g of2-(methoxycarbonyl)methoxy-3-nitropyridine.

[0245] m.p.: 61.5° C.

[0246] Step 2:

[0247] A mixture of 0.3 g of 2-(methoxycarbonyl)methoxy-3-nitropyridine,20 mg of platinum oxide, and 1.4 ml of ethanol was stirred at roomtemperature under an atmosphere of hydrogen gas for 3 hours. The gas inthe atmosphere on the reaction system was replaced with nitrogen gas,and the reaction mixture was filtered through Celite. The filtrate wasconcentrated. The residue was subjected to silica gel columnchromatography to give 0.22 g of3-amino-2-(methoxycarbonyl)methoxypyridine.

[0248]¹H-NMR(CDCl₃, 250 MHz) δ(ppm): 3.77 (s, 3H), 3.85 (bs, 2H), 4.95(s, 2H), 6.75 (dd, 1H, J=7.5, 5.0 Hz), 6.91 (dd, 1H, J=7.5, 1.6 Hz),7.50 (dd, 1H, J=5.0, 1.6 Hz).

[0249] Step 3:

[0250] First, 1.6 g of a boron trifluoride diethyl ether complex wasadded dropwise to a mixture of 1.0 g of3-amino-2-(methoxycarbonyl)methoxypyridine, 3 (ml of1,2-dimethoxyethane, and 1 ml of dichloromethane at −10° C. Afterstirring at the same temperature for 10 minutes, a solution of 0.68 g oft-butyl nitrite in 1 ml of 1,2-dimethoxyethane was added dropwise to thereaction mixture at −5° C. or lower. After stirring at the sametemperature for 30 minutes, n-pentane was poured into the mixture. Thelower one of the two layers separated was dissolved in 5 ml of aceticanhydride, and the solution was stirred at 80° C. for 1 hour. After thesolvent was distilled out, the residue was subjected to silica gelchromatography to give 0.45 g of3-acetoxy-2-(methoxycarbonyl)methoxypyridine.

[0251]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 2.33 (s, 3H), 3.75 (s, 3H), 4.92(s, 2H), 6.93 (dd, 1H, J=7.7, 5.0 Hz), 7.38 (dd, 1H, J=7.7, 1.6 Hz),7.97 (dd, 1H, J=5.0, 1.6 Hz).

[0252] Step 4:

[0253] A mixture of 0.1 g of3-acetoxy-2-(methoxycarbonyl)methoxypyridine, 31 mg of potassiumcarbonate, and 1 ml of methanol was stirred at room temperature for 3hours. The reaction mixture was poured into water, and the mixture wasextracted with ethyl acetate. The organic layer was dried over anhydrousmagnesium sulfate and then concentrated. The residue was subjected tosilica gel column chromatography to give 73 mg of3-hydroxy-2-(methoxycarbonyl)methoxypyridine.

[0254]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 3.78 (s, 3H), 4.98 (s, 2H), 6.84(dd, 1H, J=7.7, 5.0 Hz), 7.17 (dd, 1H, J=7.7, 1.3 Hz), 7.63 (dd, 1H,J=5.0, 1.3 Hz).

[0255] Step 5:

[0256] To a mixture of 0.29 g of3-hydroxy-2-(methoxycarbonyl)methoxypyridine, 0.23 g of2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene, and 3.2 ml of N,N-dimethylformamide was added0.11 g of potassium carbonate, and the mixture was stirred at 70° C. for2 hours. Another 0.12 g of2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene and another 0.05 g of potassium carbonate wereadded, and the mixture was stirred at 70° C. for 1 hour. The reactionmixture was cooled to room temperature and then poured into ice water,and the mixture was extracted with ethyl acetate. The organic layer waswashed with saturated aqueous sodium chloride solution, dried overanhydrous magnesium sulfate, and then concentrated. The residue wassubjected to silica gel column chromatography to give 0.39 g of3-{4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-2-nitrophenoxy}-2-(methoxycarbonyl)methoxypyridine.

[0257]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 3.51 (q, 3H, J=1.1 Hz), 3.68 (s,3H), 4.86 (d, 1H), 4.98 (d, 1H), 6.29 (s, 1H), 6.99 (dd, 1H, J=7.8, 4.9Hz), 7.11 (d, 1H, J=6.0 Hz), 7.51 (dd, 1H, J=7.8, 1.6 Hz), 7.87 (d, 1H,J=8.6 Hz), 7.99 (dd, 1H, J=4.9, 1.6 Hz).

[0258] Step 6:

[0259] To a mixture of 0.3 g of iron powder, 3 ml of acetic acid, and0.3 ml of water was added dropwise a solution of 0.30 g of3-{4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-2-nitrophenoxy}-2-(methoxycarbonyl)methoxypyridine in 2 ml ofacetic acid, while the temperature of the reaction mixture was kept at35° C. or lower. After completion of the dropwise addition, the mixturewas stirred for 2 hours and then filtered through Celite. The filtratewas diluted with ethyl acetate, and the mixture was neutralized withsaturated aqueous sodium bicarbonate solution. The organic layer waswashed with saturated aqueous sodium chloride solution, dried overanhydrous magnesium sulfate, and then concentrated. The residue wassubjected to silica gel column chromatography to give 0.24 g of3-{2-amino-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-(methoxycarbonyl)methoxypyridine.

[0260]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 3.52 (s, 3H), 3.74 (s, 3H), 4.29(bs, 2H), 5.00 (S, 2H), 6.30 (s, 1H), 6.61 (d, 1H, J=11.3 Hz), 6.76 (d,1H, J=6.8 Hz), 6.86 (dd, 1H, J=7.8, 5.0 Hz), 7.22 (dd, 1H, J=7.8, 1.1Hz), 7.82 (dd, 1H, J=5.0, 1.1 Hz).

[0261] Reference Production Example 11

[0262] Step 1:

[0263] First, 0.8 g of sodium hydride was added to a mixture of 3.17 gof 2-chloro-3-nitropyridine, 2.19 g of methyl lactate, and 20 ml of1,4-dioxane at 10° C., and the mixture was stirred at room temperaturefor 1.5 hours. The reaction mixture was poured into ice water, and themixture was extracted with ethyl acetate. The organic layer was driedover anhydrous magnesium sulfate and then concentrated. The residue wassubjected to silica gel column chromatography to give 3.3 g of2-{1-(methoxycarbonyl)ethoxy}-3-nitropyridine.

[0264]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 1.70 (d, 3H, J=7.0 Hz), 3.74 (s,3H), 5.46 (q, 1H, J=7.0 Hz), 7.07 (dd, 1H, J=7.8, 5.0 Hz), 8.2-8.4 (m,2H).

[0265] Step 2:

[0266] A mixture of 1.7 g of2-{1-(methoxycarbonyl)ethoxy}-3-nitropyridine, 102 mg of platinum oxide,and 7.5 ml of ethanol was stirred at room temperature under anatmosphere of hydrogen gas for 3.5 hours. The gas in the atmosphere onthe reaction system was replaced with nitrogen gas, and the reactionmixture was filtered through Celite. The filtrate was concentrated. Theresidue was subjected to silica gel column chromatography to give 1.16 gof 3-amino-2-{1-(methoxycarbonyl)ethoxy}pyridine.

[0267]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 1.63 (d, 3H, J=6.8 Hz), 3.74 (s,3H), 3.84 (bs, 2H), 5.38 (d, 1H, J=6.8 Hz), 6.72 (dd, 1H, J=7.7, 5.0Hz), 6.90 (dd, 1H, J=7.7, 1.4 Hz), 7.48 (dd, 1H, J=5.0, 1.4 Hz).

[0268] Step 3:

[0269] First, 1.5 ml of a boron trifluoride diethyl ether complex wasadded dropwise to a mixture of 1.1 g of3-amino-2-{1-(methoxycarbonyl)ethoxy}pyridine, 1 ml of1,2-dimethoxyethane, and 1 ml of dichloroethane at −10° C. Afterstirring at the same temperature for 10 minutes, a solution of 0.8 ml oft-butyl nitrite in 1 ml of 1,2-dimethoxyethane was added dropwise to thereaction mixture at −5° C. or lower. After stirring at the sametemperature for 30 minutes, n-pentane was poured into the mixture. Thelower one of the two layers separated was dissolved in acetic anhydride,and the solution was stirred at 70° C. for 1 hour. After the solvent wasdistilled out, the residue was subjected to silica gel chromatography togive 0.34 g of 3-acetoxy-2-{1-(methoxycarbonyl)ethoxy}pyridine.

[0270]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 1.60 (d, 1H, J=7.0 Hz), 2.33 (s,3H), 3.73 (s, 3H), 5.34 (q, 1H, J=7.0 Hz), 6.91 (dd, 1H, J=7.6, 5.0 Hz),7.36 (dd, 1H, J=7.6, 1.5 Hz), 7.97 (dd, 1H, J=5.0, 1.5 Hz).

[0271] Step 4:

[0272] A mixture of 0.34 g of3-acetoxy-2-{1-(methoxycarbonyl)ethoxy}pyridine, 0.11 g of potassiumcarbonate, and 2 ml of methanol was stirred at room temperature for 1hour. The reaction mixture was poured into water, and the mixture wasextracted with ethyl acetate. The organic layer was dried over anhydrousmagnesium sulfate and then concentrated. The residue was subjected tosilica gel column chromatography to give 198 mg of3-hydroxy-2-{1-(methoxycarbonyl)ethoxy}pyridine.

[0273]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 1.64 (d, 1H, J=7.0 Hz), 3.75 (s,3H), 5.45 (q, 1H, J=7.0 Hz), 6.0-6.2 (bs, 1H), 6.83 (dd, 1H, J=7.7, 5.0Hz), 7.15 (dd, 1H, J=7.7, 1.5 Hz), 7.63 (dd, 1H, J=5.0, 1.5 Hz).

[0274] Step 5:

[0275] To a mixture of 0.18 g of3-hydroxy-2-{1-(methoxycarbonyl)ethoxy}pyridine, 0.19 g of2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene, and 2.0 ml of N,N-dimethylformamide was added90 mg of potassium carbonate, and the mixture was stirred at 70° C. for3 hours. The reaction mixture was cooled to room temperature and thenpoured into ice water, and the mixture was extracted with ethyl acetate.The organic layer was washed with saturated aqueous sodium chloridesolution, dried over anhydrous magnesium sulfate, and then concentrated.The residue was subjected to silica gel column chromatography to give0.21 g of3-{4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-2-nitrophenoxy}-2-{1-(methoxycarbonyl)ethoxy}pyridine as amixture of diastereoisomers.

[0276]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 1.45 (d, 3/2H, J=7.1 Hz), 1.46 (d,3/2H, J=7.1 Hz), 3.49 (s, 3/2H), 3.51 (s, 3/2H), 3.66 (s, 3H), 5.29 (q,1/2H, J=7.1 Hz), 5.31 (q, 1/2H, J=7.1 Hz), 6.28 (s, 1/2H), 6.30 (s,1/2H), 6.9-7.0 (m, 1H), 7.10 (d, 1/2H, J=6.1 Hz), 7.17 (d, 1/2H, J=6.1Hz), 7.4-7.6 (m, 1H), 7.8-7.9 (m, 1H), 7.9-8.0 (m, 1H).

[0277] Step 6:

[0278] To a mixture of 0.21 g of iron powder, 3 ml of acetic acid, and0.3 ml of water was added dropwise a solution of3-{4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-2-nitrophenoxy}-2-{1-(methoxycarbonyl)ethoxy}pyridine in 1.2ml of acetic acid, while the temperature of the reaction mixture waskept at 35° C. or lower. After completion of the dropwise addition, themixture was stirred for 1 hour and then filtered through Celite. Thefiltrate was diluted with ethyl acetate. The mixture was neutralizedwith saturated aqueous sodium bicarbonate solution. The organic layerwas washed with saturated aqueous sodium chloride solution, dried overanhydrous magnesium sulfate, and then concentrated. The residue wassubjected to silica gel chromatography to give 0.16 g of3-{2-amino-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-{1-(methoxycarbonyl)ethoxy}pyridine as amixture of diastereoisomers.

[0279]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 1.61 (d, 3H, J=7.1 Hz), 3.52 (s,3H), 3.72 (s, 3H), 4.28 (bs, 2H), 5.40 (q, 1/2H, J=7.1 Hz), 5.41 (q,1/2H, J=7.1 Hz), 6.30 (s, 1H), 6.62 (d, 1H, J=10.9 Hz), 6.7-6.8 (m, 1H),6.8-6.9 (m, 1H), 7.2-7.3 (m, 1H), 7.7-7.9 (m, 1H).

[0280] Reference Production Example 12

[0281] Step 1:

[0282] First, 0.8 g of sodium hydride was added to a mixture of 3.17 gof 2-chloro-3-nitropyridine, 2.12 g of methyl thioglycolate, and 20 mlof tetrahydrofuran at 0° C. After stirring at room temperature for 2hours, the reaction mixture was poured into ice water, and the mixturewas extracted with ethyl acetate. The organic layer was dried overanhydrous magnesium sulfate and then concentrated. The residue waswashed with diisopropyl ether and hexane to give 3.1 g of2-(methoxycarbonyl)methylthio-3-nitropyridine.

[0283]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 3.75 (s, 3H), 3.98 (s, 2H), 7.24(dd, 1H, J=8.0, 4.8 Hz), 8.54 (dd, 1H, J=8.0, 1.8 Hz), 8.66 (dd, 1H,J=4.8, 1.8 Hz).

[0284] Step 2:

[0285] A mixture of 3.0 g of2-(methoxycarbonyl)methylthio-3-nitropyridine, 180 mg of platinum oxide,and 14 ml of ethanol was stirred at room temperature under an atmosphereof hydrogen gas for 3 hours. The gas in the atmosphere on the reactionsystem was placed with nitrogen gas, and the reaction mixture wasfiltered through Celite. The filtrate was concentrated. The residue wassubjected to silica gel column chromatography to give 2.54 g of3-amino-2-(methoxycarbonyl)methylthiopyridine.

[0286]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 3.73 (s, 3H), 4.03 (s, 2H),6.2-6.4 (b, 1H), 7.06 (dd, 1H, J=8.0, 4.9 Hz), 7.1-7.2 (bs, 1H), 7.47(dd, 1H, J=8.0, 1.4 Hz), 8.05 (dd, 1H, J=4.9, 1.4 Hz).

[0287] Step 3:

[0288] First, 1.92 g of trifluoromethanesulfonic acid was added dropwiseto a mixture of 2.54 g of 3-amino-2-(methoxycarbonyl)methylthiopyridine,6 ml of 1,2-dimethoxyethane, and 2 ml of dichloromethane at −10° C.After stirring at the same temperature for 10 minutes, a solution of1.59 g of t-butyl nitrite in 1 ml of 1,2-dimethoxyethane was addeddropwise to the reaction mixture at −5° C. or lower. After stirring atthe same temperature for 30 minutes, n-pentane was poured into themixture. The lower one of the two layers separated was dissolved in 3 mlof acetic anhydride, and the solution was stirred at 50° C. to 70° C.for 1 hour. The reaction mixture was cooled to room temperature and thenpoured into water, and the mixture was extracted with t-butyl methylether. The organic layer was washed with saturated aqueous sodiumhydrogencarbonate solution and saturated aqueous sodium chloridesolution, dried over anhydrous magnesium sulfate, and then concentrated.The residue was subjected to silica gel chromatography to give 0.48 g of3-acetoxy-2-(methoxycarbonyl)methylthiopyridine.

[0289]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 2.36 (s, 3H), 3.74 (s, 3H), 4.00(s, 2H), 7.07 (dd, 1H, J=8.0, 4.7 Hz), 7.37 (dd, 1H, J=8.0, 1.5 Hz),8.29 (dd, 1H, J=4.7, 1.5 Hz).

[0290] Step 4:

[0291] A mixture of 0.48 g of3-acetoxy-2-(methoxycarbonyl)methylthiopyridine, 0.15 g of potassiumcarbonate, and 3 ml of methanol was stirred at room temperature for 3hours. The reaction mixture was poured into water, and the mixture wasextracted with ethyl acetate. The organic layer was dried over anhydrousmagnesium sulfate and then concentrated. The residue was subjected tosilica gel column chromatography to give 0.26 g of3-hydroxy-2-(methoxycarbonyl)methylthiopyridine.

[0292]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 3.74 (s, 3H), 3.92 (s, 2H), 7.02(dd, 1H, J=8.1, 4.6 Hz), 7.13 (d, 1H, J=8.1 Hz), 8.06 (d, 1H, J=4.6 Hz).

[0293] Step 5:

[0294] To a mixture of 0.26 g of3-hydroxy-2-(methoxycarbonyl)methylthiopyridine, 0.38 g of2,5-difluoro-4-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]nitrobenzene, and 2 ml of N,N-dimethylformamide was added0.17 g of potassium carbonate, and the mixture was stirred at 70° C. for2 hours. The reaction mixture was cooled to room temperature and thenpoured into ice water, and the mixture was extracted with ethyl acetate.The organic layer was washed with saturated aqueous sodium chloridesolution, dried over anhydrous magnesium sulfate, and then concentrated.The residue was subjected to silica gel column chromatography to give0.49 g of3-{4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-2-nitrophenoxy}-2-(methoxycarbonyl)methylthiopyridine.

[0295]¹H-NMR (CDCl₃, 300 MHz) δ(ppm): 3.54 (s, 3H), 3.73 (s, 3H), 4.01(s, 2H), 6.33 (s, 1H), 7.0-7.1 (m, 2H), 7.18 (dd, 1H, J=7.8, 1.3 Hz),7.92 (d, 1H, J=8.5 Hz), 8.28 (dd, 1H, J=4.4, 1.3 Hz).

[0296] Step 6:

[0297] To a mixture of 0.5 g of iron powder, 1.5 ml of acetic acid, and0.15 ml of water was added dropwise a solution of 0.41 g of3-{4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-2-nitrophenoxy}-2-(methoxycarbonyl)methylthiopyridine in 1 mlof acetic acid, while the temperature of the reaction mixture was keptat 35° C. or lower. After completion of the dropwise addition, thereaction mixture was stirred for 2 hours and then filtered throughCelite. The filtrate was diluted with ethyl acetate. The mixture wasneutralized with saturated aqueous sodium bicarbonate solution. Theorganic layer was washed with saturated aqueous sodium chloridesolution, dried over anhydrous magnesium sulfate, and then concentrated.The residue was subjected to silica gel column chromatography to give0.36 g of3-{2-amino-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]phenoxy}-2-(methoxycarbonyl)methylthiopyridine.

[0298]¹H-NMR (CDCl₃, 250 MHz) δ(ppm): 3.53 (s, 3H), 3.75 (s, 3H), 4.02(s, 2H), 4.18 (bs, 2H), 6.32 (s, 1H), 6.66 (d, 1H, J=10.7 Hz), 6.82 (d,1H, J=6.7 Hz), 6.95 (dd, 1H, J=8.4, 4.9 Hz), 7.03 (dd, 1H, J=8.4, 1.4Hz), 8.14 (dd, 1H, J=4.9, 1.4 Hz).

[0299] Specific examples of compounds (I) are shown below. TABLE 1Compounds of formula (I-a) (compound a-1 to compound a-124) (I-a)

Compound No. A X R³ R¹  a-1 O CH H OH  a-2 O N H OH  a-3 S CH H OH  a-4S N H OH  a-5 O CH H OCH₃  a-6 O N H OCH₃  a-7 S CH H OCH₃  a-8 S N HOCH₃  a-9 O CH H OCH₂CH₃  a-10 O N H OCH₂CH₃  a-11 S CH H OCH₂CH₃  a-12S N H OCH₂CH₃  a-13 O CH H OCH₂CH₂CH₃  a-14 O N H OCH₂CH₂CH₃  a-15 S CHH OCH₂CH₂CH₃  a-16 S N H OCH₂CH₂CH₃  a-17 O CH H OCH₂CH₂CH₂CH₃  a-18 O NH OCH₂CH₂CH₂CH₃  a-19 O CH H OCH₂CH₂CH₂CH₂CH₃  a-20 O N HOCH₂CH₂CH₂CH₂CH₃  a-21 O CH H OCH₂CH═CH₂  a-22 O N H OCH₂CH═CH₂  a-23 OCH H OCH(CH₃)₂  a-24 O N H OCH(CH₃)₂  a-25 O CH H OCH₂C≡CH  a-26 O N HOCH₂C≡CH  a-27 O CH H O(c-C₅H₉)  a-28 O N H O(c-C₅H₉)  a-29 O CH HO(c-C₆H₁₁)  a-30 O N H O(c-C₆H₁₁)  a-31 O CH H OCH₂CO₂CH₃  a-32 O N HOCH₂CO₂CH₃  a-33 O CH H OC(CH₃)₂CO₂CH₃  a-34 O N H OC(CH₃)₂CO₂CH₃  a-35O CH H NH₂  a-36 O N H NH₂  a-37 S CH H NH₂  a-38 S N H NH₂  a-39 O CH HNHCH₃  a-40 O N H NHCH₃  a-41 S CH H NHCH₃  a-42 S N H NHCH₃  a-43 O CHH NHCH₂CH₃  a-44 O N H NHCH₂CH₃  a-45 S CH H NHCH₂CH₃  a-46 S N HNHCH₂CH₃  a-47 O CH H NHCH₂CH₂CH₃  a-48 O N H NHCH₂CH₂CH₃  a-49 S CH HNHCH₂CH₂CH₃  a-50 S N H NHCH₂CH₂CH₃  a-51 O CH H NHCH₂CH₂CH₂CH₃  a-52 ON H NHCH₂CH₂CH₂CH₃  a-53 O CH H NHCH₂CH₂CH₂CH₂CH₃  a-54 O N HNHCH₂CH₂CH₂CH₂CH₃  a-55 O CH H NHCH₂CH═CH₂  a-56 O N H NHCH₂CH═CH₂  a-57O CH H NHCH(CH₃)₂  a-58 O N H NHCH(CH₃)₂  a-59 O CH H NHCH₂C≡CH  a-60 ON H NHCH₂C≡CH  a-61 O CH H NH(c-C₅H₉)  a-62 O N H NH(c-C₅H₉)  a-63 O CHH NH(c-C₆H₁₁)  a-64 O N H NH(c-C₆H₁₁)  a-65 O CH H NHCH₂CO₂CH₃  a-66 O NH NHCH₂CO₂CH₃  a-67 O CH H NHC(CH₃)₂CO₂CH₃  a-68 O N H NHC(CH₃)₂CO₂CH₃ a-69 NH CH H OH  a-70 NH N H OH  a-71 NH CH H OH  a-72 NH N H OH  a-73NH CH H OCH₃  a-74 NH N H OCH₃  a-75 NH CH H OCH₃  a-76 NH N H OCH₃ a-77 NH CH H OCH₂CH₃  a-78 NH N H OCH₂CH₃  a-79 NH CH H OCH₂CH₃  a-80NH N H OCH₂CH₃  a-81 NH CH H OCH₂CH₂CH₃  a-82 NH N H OCH₂CH₂CH₃  a-83 NHCH H OCH₂CH₂CH₃  a-84 NH N H OCH₂CH₂CH₃  a-85 NH CH H OCH₂CH₂CH₂CH₃ a-86 NH N H OCH₂CH₂CH₂CH₃  a-87 NH CH H OCH₂CH₂CH₂CH₂CH₃  a-88 NH N HOCH₂CH₂CH₂CH₂CH₃  a-89 NH CH H OCH₂CH═CH₂  a-90 NH N H OCH₂CH═CH₂  a-91O CH H ONHCH₃  a-92 O N H ONHCH₃  a-93 O CH H ONHCH₂CH₃  a-94 O N HONHCH₂CH₃  a-95 O CH H ON(CH₃)₂  a-96 O N H ON(CH₃)₂  a-97 O CH HON═C(CH₃)₂  a-98 O N H ON═C(CH₃)₂  a-99 O CH H N(CH₂CH₃)₂ a-100 O N HN(CH₂CH₃)₂ a-101 O CH H N(CH₃)(CH₂CH₃) a-102 O N H N(CH₃)(CH₂CH₃) a-103O CH H NHOCH₃ a-104 O N H NHOCH₃ a-105 O CH H NHOCH₂CH₃ a-106 O N HNHOCH₂CH₃ a-107 O CH 5-Cl OCH₃ a-108 O N 5-Cl OCH₃ a-109 S CH 5-Cl OCH₃a-110 S N 5-Cl OCH₃ a-111 O CH 5-Cl OCH₂CH₃ a-112 O N 5-Cl OCH₂CH₃ a 113O CH 5-F OCH₃ a-114 O N 5-F OCH₃ a-115 O CH 5-CH₃ OCH₃ a-116 O N 5-CH₃OCH₃ a-117 O CH 5-OCH₃ OCH₃ a-118 O N 5-OCH₃ OCH₃ a-119 O CH 5-OCH₃OCH₂CH₃ a-120 O N 5-OCH₃ OCH₂CH₃ a-121 O CH H Otert-C₄H₉ a-122 O N HO-tert-C₄H₉ a-123 O CH H O-iso-C₄H₉ a-124 O N H O-iso-C₄H₉

[0300] TABLE 2 Compounds of formula (I-b) (compound b-1 to compoundb-124) (I-b)

Compound No. A X R³ R¹  b-1 O CH H OH  b-2 O N H OH  b-3 S CH H OH  b-4S N H OH  b-5 O CH H OCH₃  b-6 O N H OCH₃  b-7 S CH H OCH₃  b-8 S N HOCH₃  b-9 O CH H OCH₂CH₃  b-10 O N H OCH₂CH₃  b-11 S CH H OCH₂CH₃  b-12S N H OCH₂CH₃  b-13 O CH H OCH₂CH₂CH₃  b-14 O N H OCH₂CH₂CH₃  b-15 S CHH OCH₂CH₂CH₃  b-16 S N H OCH₂CH₂CH₃  b-17 O CH H OCH₂CH₂CHCH₃  b-18 O NH OCH₂CH₂CH₂CH₃  b-19 O CH H OCH₂CH₂CH₂CH₂CH₃  b-20 O N HOCH₂CH₂CH₂CH₂CH₃  b-21 O CH H OCH₂CH═CH₂  b-22 O N H OCH₂CH═CH₂  b-23 OCH H OCH(CH₃)₂  b-24 O N H OCH(CH₃)₂  b-25 O CH H OCH₂C═CH  b-26 O N HOCH₂C═CH  b-27 O CH H O(c-C₅H₉)  b-28 O N H O(c-C₅H₉)  b-29 O CH HO(c-C₆H₁₁)  b-30 O N H O(c-C₆H₁₁)  b-31 O CH H OCH₂CO₂CH₃  b-32 O N HOCH₂CO₂CH₃  b-33 O CH H OC(CH₃)₂CO₂CH₃  b-34 O N H OC(CH₃)₂CO₂CH₃  b-35O CH H NH₂  b-36 O N H NH₂  b-37 S CH H NH₂  b-38 S N H NH₂  b-39 O CH HNHCH₃  b-40 O N H NHCH₃  b-41 S CH H NHCH₃  b-42 S N H NHCH₃  b-43 O CHH NHCH₂CH₃  b-44 O N H NHCH₂CH₃  b-45 S CH H NHCH₂CH₃  b-46 S N HNHCH₂CH₃  b-47 O CH H NHCH₂CH₂CH₃  b-48 O N H NHCH₂CH₂CH₃  b-49 S CH HNHCH₂CH₂CH₃  b-50 S N H NHCH₂CH₂CH₃  b-51 O CH H NHCH₂CH₂CH₂CH₃  b-52 ON H NHCH₂CH₂CH₂CH₃  b-53 O CH H NHCH₂CH₂CH₂CH₂CH₃  b-54 O N HNHCH₂CH₂CH₂CH₂CH₃  b-55 O CH H NHCH₂CH═CH₂  b-56 O N H NHCH₂CH═CH₂  b-57O CH H NHCH(CH₃)₂  b-58 O N H NHCH(CH₃)₂  b-59 O CH H NHCH₂C═CH  b-60 ON H NHCH₂C═CH  b-61 O CH H NH(c-C₅H₉)  b-62 O N H NH(c-C₅H₉)  b-63 O CHH NH(c-C₆H₁₁)  b-64 O N H NH(c-C₆H₁₁)  b-65 O CH H NHCH₂CO₂CH₃  b-66 O NH NHCH₂CO₂CH₃  b-67 O CH H NHC(CH₃)₂CO₂CH₃  b-68 O N H NHC(CH₃)₂CO₂CH₃ b-69 NH CH H OH  b-70 NH N H OH  b-71 NH CH H OH  b-72 NH N H OH  b-73NH CH H OCH₃  b-74 NH N H OCH₃  b-75 NH CH H OCH₃  b-76 NH N H OCH₃ b-77 NH CH H OCH₂CH₃  b-78 NH N H OCH₂CH₃  b-79 NH CH H OCH₂CH₃  b-80NH N H OCH₂CH₃  b-81 NH CH H OCH₂CH₂CH₃  b-82 NH N H OCH₂CH₂CH₃  b-83 NHCH H OCH₂CH₂CH₃  b-84 NH N H OCH₂CH₂CH₃  b-85 NH CH H OCH₂CH₂CH₂CH₃ b-86 NH N H OCH₂CH₂CH₂CH₃  b-87 NH CH H OCH₂CH₂CH₂CH₂CH₃  b-88 NH N HOCH₂CH₂CH₂CH₂CH₃  b-59 NH CH H OCH₂CH═CH₂  b-90 NH N H OCH₂CH═CH₂  b-91O CH H ONHCH₃  b-92 O N H ONHCH₃  b-93 O CH H ONHCH₂CH₃  b-94 O N HONHCH₂CH₃  b-95 O CH H ON(CH₃)₂  b-96 O N H ON(CH₃)₂  b-97 O CH HON═C(CH₃)₂  b-98 O N H ON═C(CH₃)₂  b-99 O CH H N(CH₂CH₃)₂ b-100 O N HN(CH₂CH₃) b-101 O CH H N(CH₃)(CH₂CH₃) b-102 O N H N(CH₃)(CH₂CH₃) b-103 OCH H NHOCH₃ b-104 O N H NHOCH₃ b-105 O CH H NHOCH₂CH₃ b-106 O N HNHOCH₂CH₃ b-107 O CH 5-Cl OCH₃ b-108 O N 5-Cl OCH₃ b-109 S CH 5C1 OCH₃b-110 S N 5C1 OCH₃ b-111 O CH 5-Cl OCH₂CH₃ b-112 O N 5-Cl OCH₂CH₃ b-113O CH 5-F OCH₃ b-114 O N 5-F OCH₃ b-115 O CH 5-CH₃ OCH₃ b-116 O N 5-CH₃OCH₃ b-117 O CH 5-OCH₃ OCH₃ b-118 O N 5-OCH₃ OCH₃ b-119 O CH 5-OCH₃OCH₂CH₃ b-120 O N 5-OCH₃ OCH₂CH₃ b-121 O CH H O-tert-C₄H₉ b-122 O N HO-tert-C₄H₉ b-123 O CH H O-iso-C₄H₉ b-124 O N H O-iso-C₄H₉

[0301] TABLE 3 Compounds of formula (I-c) (compound c-1 to compoundc-48) (I-c)

Compound No. Z X R³ R¹ c-1 Br CH H OH c-2 Br N H OH c-3 Br CH CH₃ OH c-4Br N CH₃ OH c-5 Br CH H OCH₃ c-6 Br N H OCH₃ c-7 Br CH CH₃ OCH₃ c-8 Br NCH₃ OCH₃ c-9 Br CH H OCH₂CH₃ c-10 Br N H OCH₂CH₃ c-11 Br CH CH₃ OCH₂CH₃c-12 Br N CH₃ OCH₂CH₃ c-13 Br CH H OCH₂CH₂CH₃ c-14 Br N H OCH₂CH₂CH₃c-15 Br CH CH₃ OCH₂CH₂CH₃ c-16 Br N CH₃ OCH₂CH₂CH₃ c-17 Br CH HOCH₂CH₂CH₂CH₂CH₃ c-18 Br N H OCH₂CH₂CH₂CH₂CH₃ c-19 Br CH CH₃OCH₂CH₂CH₂CH₂CH₃ c-20 Br N CH₃ OCH₂CH₂CH₂CH₂CH₃ c-21 Br CH H O(c-C₅H₉)c-22 Br N H O(c-C₅H₉) c-23 Br CH CH₃ O(c-C₅H₉) c-24 Br N CH₃ O(c-C₅H₉)c-25 F CH H OCH₃ c-26 F N H OCH₃ c-27 F CH CH₃ OCH₃ c-28 F N CH₃ OCH₃c-29 F CH H OCH₂CH₃ c-30 F N H OCH₂CH₃ c-31 F CH CH₃ OCH₂CH₃ c-32 F NCH₃ OCH₂CH₃ c-33 F CH H OCH₂CO₂CH₃ c-34 F N H OCH₂CO₂CH₃ c-35 F CH HOC(CH₃)₂CO₂CH₃ c-36 F N H OC(CH₃)₂CO₂CH₃ c-37 I CH H OCH₃ c-38 I N HOCH₃ c-39 I CH CH₃ OCH₃ c-40 I N CH₃ OCH₃ c-41 I CH H OCH₂CH₃ c-42 I N HOCH₂CH₃ c-43 I CH CH₃ OCH₂CH₃ c-44 I N CH₃ OCH₂CH₃ c-45 Br CH H NH₂ c-46Br N H NH₂ c-47 Br CH H NHCH₃ c-48 Br N H NHCH₃

[0302] The following will describe formulation examples. In theseformulation examples, “parts” represents parts by weight.

Formulation Example 1

[0303] Fifty parts of each of compounds a-1 to a-124, compounds b-1 tob-124, and compounds c-1 to c-48, 3 parts of calcium lignin sulfonate, 2parts of sodium lauryl sulfate, and 45 parts of synthetic hydratedsilicon oxide are well pulverized and mixed to give a wettable powderfor each compound.

Formulation Example 2

[0304] Seventy parts of each of compounds a-1 to a-124, compounds b-1 tob-124, and compounds c-1 to c-48, 3 parts of calcium lignin sulfonate, 2parts of sodium lauryl sulfate, and 25 parts of synthetic hydratedsilicon oxide are well pulverized and mixed to give a wettable powderfor each compound.

Formulation Example 3

[0305] Twenty parts of each of compounds a-1 to a-124, compounds b-1 tob-124, and compounds c-1 to c-48, 3 parts of polyoxyethylene sorbitanmonooleate, 3 parts of CMC (carboxymethylcellulose), and 74 parts ofwater are mixed and wet pulverized so that the mean particle size comesto 5 μm or smaller to give a flowable of each compound.

Formulation Example 4

[0306] Forty parts of each of compounds a-1 to a-124, compounds b-1 tob-124, and compounds c-1 to c-48, 3 parts of polyoxyethylene sorbitanmonooleate, 3 parts of CMC (carboxymethylcellulose), and 54 parts ofwater are mixed and wet pulverized so that the mean particle size comesto 5 μm or smaller to give a flowable of each compound.

[0307] The following will describe test example and the presentinvention should not be limited to the test example.

[0308] Test Example

[0309] Seed potatoes were planted on a field and grown. At the time ofthe foliage turning yellow, 2.5 parts of each of compounds a-5 and a-6,10 parts of Sorpol 3890 (Toho Chemical Industry Co., Ltd.), and 87.5parts of SOLVESSO 200 (Exxon Mobile Chemical Company) were well mixed togive an emulsifiable concentrate for each compound, diluted at aprescribed dose with water containing 1% (v/v) crop oil concentrate(COC), and the dilution was uniformly sprayed to the plants. One sectionof the treated field are 2.1×15.2 m in area, and the potato plants on 14day after the treatment were examined for the desiccant effect. Theresults are shown in Table 4. In the table, the desiccation effect wasevaluated with following criteria.

[0310] Evaluating criteria

[0311] 1: The desiccated area of foliage is 0 to 29%

[0312] 2: The desiccated area of foliage is 30 to 69%

[0313] 3: The desiccated area of foliage is 70 to 89%

[0314] 4: The desiccated area of foliage is 90 to 99%

[0315] 5: The desiccated area of foliage is 100%

[0316] The treatment was done in 3 sections, the result was indicatedwith an average of the 3 sections. TABLE 4 Application amountDesiccation Test compound (g/ha) effect Compound a-5 10 5 Compound a-610 5

INDUSTRIAL APPLICABILITY

[0317] The use of the present desiccant on a suitable time prior toharvest can gain the plants whose aboveground parts is sufficientlydesiccated on the harvest time, so that works on and/or after theharvest can easily be performed.

1. A desiccant for a crop plant, which comprises as an activeingredient, a compound of formula (I):

wherein X is CH or nitrogen; Z is halogen; A is oxygen, sulfur, or NH;R¹ is hydroxyl, C₁-C₇ alkoxy, C₃-C₇ alkenyloxy, C₃-C₇ alkynyloxy, C₅-C₇cycloalkoxy, {(C₁-C₇ alkoxy)carbonyl} C₁-C₃ alkoxy, (C₁-C₇alkylamino)oxy, {di(C₁-C₇ alkyl)amino}oxy, (C₃-C₇ alkylideneamino)oxy,C₁-C₇ alkylamino, di(C₁-C₇ alkyl)amino, C₃-C₇ alkenylamino, C₃-C₇alkynylamino, C₅-C₇ cycloalkylamino, {(C₁-C₇ alkoxy)carbonyl} C₁-C₃alkylamino, or (C₁-C₇ alkoxy)amino; R² is hydrogen or methyl; and R³ ishydrogen, halogen, C₁-C₃ alkyl, or C₁-C₃ alkoxy.
 2. The desiccant for apotato, sunflower, soybean, rape or sorghum plant, which comprises asthe active ingredient, the compound of formula (I) according to claim 1.3. The desiccant for a potato plant, which comprises as the activeingredient, the compound of formula (I) according to claim
 1. 4. Thedesiccant for a sunflower plant, which comprises the active ingredient,the compound of formula (I) according to claim
 1. 5. A method fordesiccating a crop plant, which comprises applying the compound offormula (I) according to claim 1 to the crop plant prior to harvest. 6.The method for desiccating a potato, sunflower, soybean, rape or sorghumplant, which comprises applying the compound of formula (I) according toclaim 1 to the plant prior to harvest.
 7. The method for desiccating apotato plant, which comprises applying the compound of formula (I)according to claim 1 to a aboveground part of the plants prior toharvest.
 8. The method for desiccating a sunflower plant, whichcomprises applying the compound of formula (I) according to claim 1 to aaboveground part of the sunflower plant prior to harvest.
 9. The methodaccording to any one of claims 5 to 8, wherein the compound of formula(I) is applied in an amount of 1 to 500 g per 1 ha.
 10. A method forharvesting a crop, which comprises a step of applying a compound offormula (I) according to claim 1 to the crop plant.
 11. The method forharvesting a crop selecting from a group of potato, sunflower, soybean,rape and sorghum, which comprises a step of applying the compound offormula (I) according to claim 1 to the crop plant.
 12. The method forharvesting a potato, which comprises a step of applying the compound offormula (I) according to claim 1 to the potato plant.
 13. The method forharvesting a sunflower, which comprises a step of applying the compoundof formula (I) according to claim 1 to the sunflower plant.
 14. Themethod according to any one of claims 10 to 13, wherein the compound offormula (I) is applied in an amount of 1 to 500 g per 1 ha.
 15. Use of acompound of formula (I) according to claim 1 as a desiccant.